Background:Cucurbita maxima plant materials are frequently used to manage a number of disorders,according to previous studies.Objective:The goal of the present report was to look into further possible effects of this ...Background:Cucurbita maxima plant materials are frequently used to manage a number of disorders,according to previous studies.Objective:The goal of the present report was to look into further possible effects of this plant on kidney disorder in rats brought on by diabetes as well as the related abnormalities in lipid metabolism.Methods:To assess the ameliorative effect of the plant,streptozotocin(STZ)(45 mg/kg/day)was given as a single dosage to cause type 1 diabetes.After then,diabetic rats received supplemented diets of Cucurbita maxima for four weeks at 5%,10%,15%and 20%ad libidium.However,in another experiment to evaluate the preventive capacity of Cucurbita maxima,the STZ-induction came at the end of four weeks supplementation.Blood and kidney tissues were obtained at the end of the treatments and investigated.Consequently,the analysis of kidney function and lipid profile was made using serum obtained from the blood sample.Histological change in kidney was also observed using haematoxylin and eosin stain Results:Our findings demonstrated that Cucurbita maxima drastically(P<0.05)decreased the elevated kidney indicators such as urea and creatinine in the blood,and restored the electrolytes and lipid profiles anomalies as compared to the normal control.However,the alteration of biochemical parameters in the STZ-induced diabetic control remained unchanged throughout as compared to the normal control.The above mentioned biochemical changes that took place in kidney tissues were further corroborated by histological alterations.Conclusion:The results suggest that Cucurbita maxima leaves supplemented diets reversed STZ-induced renal disorder and abnormal lipid metabolism,and that these effects may be mediated by interacting with multiple receptors to raise the levels of antioxidant enzymes in the system.展开更多
AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl trans...AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl transferase(HPRT),ribosomal protein large P0(36B4)and terminal uridylyl transferase 1(U6)in the diabetic retinal tissue of rat model.METHODS:The expression of these seven genes in rat retinal tissues was determined using real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)in two groups;normal control rats and streptozotocininduced diabetic rats.The stability analysis of gene expression was investigated using geNorm,NormFinder,BestKeeper,and comparative delta-Ct(ΔCt)algorithms.RESULTS:The 36B4 gene was stably expressed in the retinal tissues of normal control animals;however,it was less stable in diabetic retinas.The 18s gene was expressed consistently in both normal control and diabetic rats’retinal tissue.That this gene was the best reference for data normalisation in RT-qPCR studies that used the retinal tissue of streptozotocin-induced diabetic rats.Furthermore,there was no ideal gene stably expressed for use in all experimental settings.CONCLUSION:Identifying relevant genes is a need for achieving RT-qPCR validity and reliability and must be appropriately achieved based on a specific experimental setting.展开更多
BACKGROUND In recent years,studies have found that the occurrence and development of diabetic cardiomyopathy(DCM)is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1(PARP-1)activity.PARP-...BACKGROUND In recent years,studies have found that the occurrence and development of diabetic cardiomyopathy(DCM)is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1(PARP-1)activity.PARP-1 activation could be involved in the pathophysiological process of DCM by promoting oxidative stress,the inflammatory response,apoptosis and myocardial fibrosis.AIM To investigate the mechanism of liraglutide in improving myocardial injury in type 2 diabetic rats,further clarified the protective effect of liraglutide on the heart,and provided a new option for the treatment of DCM.METHODS Forty healthy male SD rats aged 6 wk were randomly divided into two groups,a normal control group(n=10)and a model group(n=30),which were fed an ordinary diet and a high-sugar and high-fat diet,respectively.After successful modeling,the rats in the model group were fed a high-glucose and high-fat diet for 4 wk and randomly divided into a model group and an intervention group(further divided into a high-dose group and a low-dose group).The rats were fed a high-glucose and high-fat diet for 8 wk and then started drug intervention.Blood samples were collected from the abdominal aorta to detect fasting blood glucose and lipid profiles.Intact heart tissue was dissected,and its weight was used to calculate the heart weight index.Haematoxylin and eosin staining was used to observe the pathological changes in the myocardium and the expression of PARP-1 in the heart by immunohistochemistry.RESULTS The body weight and heart weight index of rats in the model group were significantly increased compared with those in the normal control group,and those in the intervention group were decreased compared with those in the model group,with a more obvious decrease observed in the high-dose group(P<0.05).In the model group,myocardial fibers were disordered,and inflammatory cells and interstitial fibrosis were observed.The cardiomyopathy of rats in the intervention group was improved to different degrees,the myocardial fibers were arranged neatly,and the myocardial cells were clearly striated;the improvement was more obvious in the high-dose group.Compared with the normal control group,the expression of PARP-1 in myocardial tissue of the model group was increased,and the difference was statistically significant(P<0.05).After liraglutide intervention,compared with the model group,the expression of PARP-1 in myocardial tissue was decreased,and the reduction was more obvious in the high-dose group(P<0.05)but still higher than that in the normal control group.CONCLUSION Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial PARP-1 in a dose-dependent manner.展开更多
AIM:To investigate the aldose reductase(AR)inhibition capacity of astragalin(AST)against streptozoticin-induced diabetic cataracts(DCs)in rats.METHODS:Ex vivo investigations were conducted by treating the lens of a go...AIM:To investigate the aldose reductase(AR)inhibition capacity of astragalin(AST)against streptozoticin-induced diabetic cataracts(DCs)in rats.METHODS:Ex vivo investigations were conducted by treating the lens of a goat placed for 72h in artificial aqueous humor(AAH)of pH 7.8 at room temperature with cataract-causing substance(55 mmol/L of galactose)and in vivo studies were performed on rats via induction with streptozotocin.AST was administered at different dose levels and scrutinize for DC activity.RESULTS:In diabetic rats,AST improved the body weight,blood insulin,and glucose as well as the levels of galactitol in a dose-dependent way,other biochemical parameters i.e.inflammatory mediators and cytokines,and also suppress AR activity.The level of the antioxidant parameters such as superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)activity were also altered on a diabetic lens after the administration of the AST.CONCLUSION:AST protects against lens opacification to avoid cataracts and polyols formation,indicating that it could be used as a potential therapeutic agent for diabetes.展开更多
Objective: The present study consisted of challenging the extract of kombucha and the fungus Ganoderma reported as hypoglycemic and used as alternative treatments against diabetes on the number and morphology of islet...Objective: The present study consisted of challenging the extract of kombucha and the fungus Ganoderma reported as hypoglycemic and used as alternative treatments against diabetes on the number and morphology of islets of Langerhans. Material and Methods: 64 Wistar rats were used in 4 groups: one control, three experimental, streptozotocin, Kombucha y Ganoderma induced diabetes with streptozotocin. Divided into four post-induction stages at 2, 15, 30 and 45 days of treatment, sacrificing 4 rats at each stage, to perform the morphological analysis of the pancreas. Results: A decrease in the islets of Langerhans in size, volume and the number of cells within them was identified for the streptozotocin group from the second stage until almost disappearing due to diabetes, in the groups of Kombucha y Ganoderma the same was observed but they were recovered with the extract treatments and the average number of islets was similar in these groups, the group of Ganoderma. Conclusion: Under the conditions of this work, a protective and regenerative effect of both extracts is identified.展开更多
AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biolog...AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells(HRMEC)under high glucose conditions was tested by a cell counting kit,wound healing,a transwell and a tube formation assay.The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction(RT-PCR).The expression of the cell junction was measured by Western blotting(WB)and immunofluorescence staining.In addition,two groups of rat models,diabetic and non-diabetic,were fed with normal or 0.1%TMAO for 16wk,and their plasma levels of TMAO,vascular endothelial growth factor(VEGF),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere tested.The vascular permeability of rat retinas was measured using FITC-Dextran,and the expression of zonula occludens(ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining.RESULTS:TMAO administration significantly increased the cell proliferation,migration,and tube formation of primary HRMEC either in normal or high-glucose conditions.RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation,while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment.Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage,which were even higher in TMAO-feeding diabetic rats.Furthermore,TMAO administration increased the rat plasma levels of VEGF,IL-6 and TNF-αwhile decreasing the retinal expression levels of ZO-1 and claudin-5.CONCLUSION:TMAO enhances the proliferation,migration,and tube formation of HRMEC,as well as destroys their vascular integrity and tight connection.It also regulates the expression of VEGF,IL-6,and TNF-α.展开更多
Objective To investigate the renal protective activity of Hsian-tsao Mesona procumbens Hemsl. water extracts in diabetic rats. Methods Thirty Sprague-dawley female rats were randomly divided into three groups (n=10 e...Objective To investigate the renal protective activity of Hsian-tsao Mesona procumbens Hemsl. water extracts in diabetic rats. Methods Thirty Sprague-dawley female rats were randomly divided into three groups (n=10 each), "control group" with intraperitoneal saline injection, "diabetic group" with 60 mg of intraperitoneal streptozotocin injection per kg of body weight and "Hsian-tsao group" with intragastric administration of Hsian-tsao extraction everyday for 4 weeks after intraperitoneal streptozotocin injection. The body weight and blood sugar were measured before and after model induction in the three groups. Thrombospondin-1 (TSP-1) expressions in the kidney were monitored by immunohistochemistry. Kidney ultrastructural changes were also analyzed by using transmission electron microscopy. Results Before diabetic model induction, there were no significant differences among the three groups in body weight and blood sugar. Four weeks after the induction of diabetes, the differences became statistically significant. Electron microscopy also revealed disruption of the foot processes of the podocytes and other damages in diabetic group. These damages were significantly less severe in Hsian-tsao group when compared with the diabetic group. TSP-1 expressions in the kidney were significantly increased in both the diabetic group and Hsian-tsao group, but it was relatively lower in Hsian-tsao group than in diabetic group. Conclusion Our results showed that Hsian-tsao treatment in the diabetic rats effectively prevented the pathological alterations in the kidney and decreased the TSP- 1 expression. It was suggested that Hsian-tsao had protective effect on the kidneys of the diabetic rats.展开更多
Objective:To investigate the antidiabetic properties of aqueous extract of stem bark of Afzelia africana(A.africana)and its beneficial effect on haematological parameters in streptozotocin induced diabetic rats.Method...Objective:To investigate the antidiabetic properties of aqueous extract of stem bark of Afzelia africana(A.africana)and its beneficial effect on haematological parameters in streptozotocin induced diabetic rats.Methods:A total of 30 rats including 24 diabetic and 6 normal rats were used for this study.Diabetes was induced in male Wistar rats by intraperitoneal injection of streptozotocin.After being confirmed diabetic,animals were orally treated with distilled water or extracts at 100 or 200 mg/kg body weight daily for 10 days.The haematological parameters including red blood and white blood cells and their functional indices were evaluated in diabetic treated groups compared with the controls.Results:The extract significantly reduced the blood glucose levels while the best result was obtained at 200 mg/kg body weight The feed and water intake in diabetic rats were significantly reduced while weight loss was minimized at both dosages.Similarly,the levels of red blood,white blood cells and their functional indices were significantly improved after extract administration at both doses.Conclusions:It can be concluded that the aqueous extract of bark of A.africana possesses antihyperglycemic properties.In addition,the extract can prevent various complications of diabetes and improve some haematological parameters.Further experimental investigation is needed to exploit its relevant therapeutic effect to substantiate its ethnomedicinal usage.展开更多
Objective:To investigate the role of red palm oil(RPO),rooibos tea extract(RTE)and their combined treatment(RPO+RTE)on antioxidant status in streptozotocin(STZ)-induced diabetic rats.Methods:Diabetes mellitus was indu...Objective:To investigate the role of red palm oil(RPO),rooibos tea extract(RTE)and their combined treatment(RPO+RTE)on antioxidant status in streptozotocin(STZ)-induced diabetic rats.Methods:Diabetes mellitus was induced by a single administration of streptozotocin(50 mg/kg)and the rats were treated for 7 weeks.Antioxidant enzymes[calalase(CAT),glutathione peroxidase(GPx),superoxide dismutase(SOD)],antioxidant capacity[trolox equivalence antioxidant capacity(TEAC),oxygen radical absorbance capacity(ORAC)]as well as total protein,albumin,globulin,total glutathione,conjugated diene and thiobarbituric acid reactive substances(TBARS)were investigated.Results:Treatment with RPO,RTE and RPO+RTE significantly(p>0.05)improved liver SOD and plasma ORAC in the diabetic rats.Similarly,diabetic rats treated with RTE and RPO+RTE enhanced liver GPx.A significant(P<0.05)increase in the plasma TBARS in the diabetic control group was observed when compared with the normal control group.Treatment of diabetic rats with RTE and RPO+RTE reduced plasma TBARS to a level not significantly different at P<0.05 from the normal control group.Conclusions:The results revealed the anti-oxidative potentials of red palm oil,rooibos and their combination in diabetic conditions and hence,they could be useful in the management of diabetes and its complications.展开更多
Objective:To evaluate the antidiabetic and antioxidant potential of Emblica officinalis(E.officinalis)fruit on normal and type 2 diabetic rats.Methods:Type 2 diabetes was induced into the male Long-Evans rats.The rats...Objective:To evaluate the antidiabetic and antioxidant potential of Emblica officinalis(E.officinalis)fruit on normal and type 2 diabetic rats.Methods:Type 2 diabetes was induced into the male Long-Evans rats.The rats were divided into nine groups including control groups receiving water,type 2 diabetic controls,type 2 diabetic rats treated with glibenclamide(T2GT)and type 2diabetic rats treated with aqueous extract of fruit pulp of E.officinalis.They were fed orally for8 weeks with a single feeding.Blood was collected by cutting the tail tip on 0 and 28 days and by decapitation on 56 day.Packed red blood cells and serum were used for evaluating different biochemical parameters.Results:Four weeks administration of aqueous extract of E.officinalis improved oral glucose tolerance in type 2 rats and after 8 weeks it caused significant(P<0.007)reduction in fasting serum glucose level compared to 0 day.Triglycerides decreased by 14%but there was no significant change in serum ALT,creatinine,cholesterol and insulin level in any group.Furthermore,reduced erythrocyte malondialdehyde level showed no significant change(P<0.07)but reduced glutathione content was found to be increased significantly(P<0.05).Conclusions:The aqueous extract of E.officinalis has a promising antidiabetic and antioxidant properties and may be considered for further clinical studies in drug development.展开更多
AIM: To evaluate the effects of etanercept on the expression of Fas, tumor necrosis factor-alpha(TNF-α) and caspase-8 in the early stage of the apoptotic pathway in diabetic rats, and to explore the therapeutic effec...AIM: To evaluate the effects of etanercept on the expression of Fas, tumor necrosis factor-alpha(TNF-α) and caspase-8 in the early stage of the apoptotic pathway in diabetic rats, and to explore the therapeutic effect of etanercept on diabetic retinopathy.METHODS: A total of 60 Sprague-Dawley(SD) rats were randomly and evenly divided into 3 groups with 20 rats each, including control group, and diabetic groups with or without treatment. Streptozotocin(STZ)-induced diabetic rats were established for diabetic groups. Blood glucose and body weight were measured weekly. All the rats were sacrificed at the 12 wk after treatment. The expressions of Fas, TNF-α and caspase-8 in rat retina were quantitatively detected by PCR and Western blot. The leakage of Evan blue was adopted to measure the retinal vascular leakage quantitatively, and to compare it among different groups. TUNEL method was used to compare the amount of apoptotic bodies quantitatively in rat retina ganglion cells under electron microscope.RESULTS: The expressions of Fas, TNF-α and caspase-8 in each group were compared via PCR and Western blot, in which the diabetic group with treatment was lower than those without treatment(P<0.01), but all the diabetic groups were higher than the control group(P<0.01). Evans blue leakage in the diabetic treatment group was lower than those without treatment(P<0.01), but those in the control group was the lowest compared with the other two groups(P<0.01). TUNEL method showed that the apoptoticbodies of retina in the diabetic treatment group was lower than those without treatment(P<0.01), while those in the control group was the lowest compared with the other two groups(P<0.01). CONCLUSION: Etanercept can effectively reduce the expression of Fas, TNF-α and caspase-8, as well as the retinal leakage and retinal cell apoptosis in diabetic rats.展开更多
An Otsuka Long-Evans Tokushima Fatty(OLETF)rat provides a useful model for studies to develop corneal wound healing drugs for use in diabetic keratopathy resulting from type 2 diabetes mellitus.We investigated the eff...An Otsuka Long-Evans Tokushima Fatty(OLETF)rat provides a useful model for studies to develop corneal wound healing drugs for use in diabetic keratopathy resulting from type 2 diabetes mellitus.We investigated the effects of sericin on corneal wound healing in OLETF rats.Corneal wounds were prepared by removal of the corneal epithelium and documented using a TRC-50X.Sericin was instilled into the eyes of rats five times a day following corneal abrasion.The plasma levels of glucose,triglycerides,cholesterol and insulin in 38 wk old OLETF rats were significantly higher than in normal control rats(LETO rats),and the rate of corneal wound healing in OLETF rats was slower than in normal rat,probably due to the suppression of cell migration and proliferation caused by high plasma glucose levels.The corneal wounds of OLETF rats instilled with saline showed almost complete healing 72h after corneal epithelial abrasion.On the other hand,the instillation of sericin has a potent effect in promoting wound healing and wound size reduction in OLETF rats and the wounds showed almost complete healing at 48 h after abrasion.The sericin may be an effective and safe drug to promote corneal wound healing in diabetic keratopathy.展开更多
AIM: To evaluate effects of Danhong Huayu Koufuye (DHK, a Chinese medicinal formulae) alone or combined with metformin on diabetic retinopathy (DR) in Zucker diabetic fatty (ZDF) rats, an animal model of obese type -2...AIM: To evaluate effects of Danhong Huayu Koufuye (DHK, a Chinese medicinal formulae) alone or combined with metformin on diabetic retinopathy (DR) in Zucker diabetic fatty (ZDF) rats, an animal model of obese type -2 diabetes, and then to investigate the mechanisms. METHODS: ZDF (fa/fa) rats were administered with vehicle (distilled water), metformin, DHK, and DHK plus metformin. Electrophysiological and histological analysis were applied to evaluated effects of DHK alone or combined with metformin on DR. The levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of DHK. Furthermore, levels of nitric oxide (NO), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum were measured to study effects of DHK on oxidative stress in ZDF rats. In addition, body weight, lipidic indexes and insulin level were also assessed. RESULTS: DHK combined with metformin significantly reversed the prolongation of latency times of flash electroretinogram (FERG) and oscillatory potentials (OPs) in diabetic rats. Furthermore, DHK alone or combined with metformin showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, DHK alone or plus metformin reduced FBG (P<0.05), HbA1c 1094 (P<0.01) and MDA (P<0.01) levels in diabetic rats. In addition, reductions in levels of triglycerides (TG) (P<0.01) and low density lipoprotein cholesterol (LDL-c) (P<0.01 and P<0.05, respectively) were also observed in diabetic rats treated with DHK alone or plus metformin. CONCLUSION: DHK in combination with metformin had a preventive and therapeutic effect on DR in type-2 diabetic rats, and the possible mechanisms may be alleviating hyperglycemia, reducing oxidative stress and improving lipid metabolism.展开更多
AIM: To evaluate the effect of β-elemene on the expressions of hypoxia-inducible factor(HIF)-lα, vascular endothelial growth factor(VEGF) and inducible nitric oxide synthase(i NOS) in a streptozotocin(STZ) induced d...AIM: To evaluate the effect of β-elemene on the expressions of hypoxia-inducible factor(HIF)-lα, vascular endothelial growth factor(VEGF) and inducible nitric oxide synthase(i NOS) in a streptozotocin(STZ) induced diabetic SpragueDawley(SD) rat model.METHODS: SD rats were administered an abdominal injection of STZ and induced to a diabetic model. After 6 wk course of diabetes, the treatment groups were given β-elemene through periocular and intravitreous injection separately and the control groups were given blank emulsion injection. HE staining was used to observe the morphology of retina. The m RNA expressions of HIF-1α, VEGF and i NOS was assayed by real-time polymerase chain reaction(PCR) and the protein expression was measured by Western blot and immunocytochemistry methods.RESULTS: The results indicated that the protein and m RNA expressions of HIF-1α, VEGF and i NOS after treated by β-elemene periocularly and intravitreally injections were all found to be reduced compared with the levels in the diabetic rats group(P<0.05). The inhibitory effect of intravitreal injection was more remarkable.CONCLUSION: The results show β-elemene protect the retina of diabetic rats from high glucose damage by downregulating the expression of HIF-1α, VEGF and iNOS.展开更多
AIM: To investigate the effect of angiotensin II type 1 receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) on intraocular growth factors and their receptors in streptozotocin-induced diabet...AIM: To investigate the effect of angiotensin II type 1 receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS: Forty Sprague-Dawley rats were divided into 4 groups: control, diabetes mellitus (DM), candesartan- treated DM, and enalapril-treated DM (each group, n---10). After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/(kg · d)] and enalapril [ACEI, 10 mg/(kg · d)] were administered to rats orally for 4Wko Vascular endothelial growth factor (VEGF) and angiotensin II (Ang II) concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor (ATIR) levels were assessed at week 4 by Western blotting. RESULTS: Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control (P=0.04 and 0.005, respectively). Vitreous ATIR increased significantly in DM compared to the other three groups (P〈0.007). Candesartan-treated DM rats showed higher vitreal ATIR concentration than the enalapril-treated DM group and control (P〈0.001 and P=0.005, respectively). No difference in vitreous Ang II and ATIR concentration was found between the enalapril- treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION: Increased Ang II and ATIR in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.展开更多
AIM:To generate phasic and tonic stress-strain curves for evaluation of intestinal smooth muscle function in type 2 diabetic rats during active and passive conditions.METHODS:Seven diabetic Goto-Kakizaki(GK)male rats,...AIM:To generate phasic and tonic stress-strain curves for evaluation of intestinal smooth muscle function in type 2 diabetic rats during active and passive conditions.METHODS:Seven diabetic Goto-Kakizaki(GK)male rats,32-wk old(GK group),and 9 age-matched normal Wistar rats(Normal group)were included in the study.Jejunal segments were distended up to a pressure of10 cm H2O in an organ bath containing 37℃Krebs solution with addition of carbachol(CA).The pressure and outer diameter changes were synchronously recorded.Passive conditions were obtained using calcium-free Krebs solution containing ethylene glycol tetraacetic acid and papaverine.Total phasic,tonic and passive circumferential stress and strain were computed from the diameter and pressure data with reference to the zero-stress state geometry.The active phasic and tonic stresses were defined as the total phasic and tonic stresses minus the passive stress.RESULTS:Diabetes increased jejunal mucosa and muscle layer thicknesses compared to the Normal group(mucosa,755.8±63.3 vs 633.1±59.1μm,P<0.01;muscle,106.3±12.9 vs 85.2±11.7μm,P<0.05).The pressure and stress thresholds were decreased in the GK group after CA application compared to distensions without CA application(pressure,1.01±0.07vs 1.99±0.19 cmH2O,P<0.01;stress,0.11±0.01vs 0.24±0.02 kPa,P<0.01).CA application did not change the pressure and stress threshold in the Normal group(pressure,2.13±0.32 vs 2.34±0.32 cm H2O,P>0.05;stress,0.25±0.03 vs 0.35±0.06 kPa,P>0.05).The amplitude of total phasic,total tonic,active phasic and active tonic circumferential stresses did not differ for the distensions without CA application between the GK group and the Normal group.However,the total phasic and total tonic stresses increased after CA application in the GK group compared those in the Normal group.When normalized to muscle layer thickness,the amplitude of active stresses before CA application was lowest in the GK group compared with the Normal group.No difference was found during CA application.CONCLUSION:The stress generated by intestinal muscle normalized to the muscle layer thickness was lowest in GK rats compared to normal rats whereas the response to CA stimulation was preserved.展开更多
Objective:To investigate the hypoglycemic effect of the aqueous extract of Octomeles sumatrana (O.sumatrana)(OS) in streptozotocin-induced diabetic rats(STZ) and its molecular mechanisms. Methods:Diabetes was induced ...Objective:To investigate the hypoglycemic effect of the aqueous extract of Octomeles sumatrana (O.sumatrana)(OS) in streptozotocin-induced diabetic rats(STZ) and its molecular mechanisms. Methods:Diabetes was induced by intraperitoneal(i.p.) injection of streptozotocin(55 mg/kg) in to male Sprague-Dawley rats.Rats were divided into six different groups;normal control rats were not induced with STZ and served as reference,STZ diabetic control rats were given normal saline.Three groups were treated with OS aqueous extract at 0.2,0.3 and 0.5 g/kg,orally twice daily continuously for 21 d.The fifth group was treated with glibenclamide(6 mg/kg) in aqueous solution orally continuously for 21 d.After completion of the treatment period,biochemical parameters and expression levels of glucose transporter 2(Slc2a2),glucose-6-phosphatase (GoPase) and phosphoenolpyruvate carboxykinase(PCK1) were determined in liver by quantitative real time PCR.Results:Administration of OS at different doses to STZ induced diabetic rats, resulted in significant decrease(P【0.05) in blood glucose level in a dose dependent manner by 36%,48%,and 64%at doses of 0.2,0.3 and 0.5 g/kg,respectively,in comparison to the STZ control values.Treatment with OS elicited an increase in the expression level of Slc2a2 gene but reduced the expression of G6Pase and PCK1 genes.Morefore,OS treated rats,showed significantly lower levels of serum alanine transaminase(ALT),aspartate aminotransferase(AST) and urea levels compared to STZ untreated rats.The extract at different doses elicited signs of recovery in body weight gain when compared to STZ diabetic controls although food and water consumption were significantly lower in treated groups compared to STZ diabetic control group.Conclusions:O.sumatrana aqueous extract is beneficial for improvement of hyperglycemia by increasing gene expression of liver Slc2a2 and reducing expression of G6Pase and PCK1 genes in streptozotocin-induced diabetic rats.展开更多
AIM: To study the histopathological changes in the retina and flash electroretinogram (F-ERG) features of ozone-treated streptozotocin (STZ)-induced diabetic rats. METHODS: Seventy male Sprague Dawley rats were ...AIM: To study the histopathological changes in the retina and flash electroretinogram (F-ERG) features of ozone-treated streptozotocin (STZ)-induced diabetic rats. METHODS: Seventy male Sprague Dawley rats were grouped as follows: blank group (GB, n=10), model control group (GM, n=18), ozone group (GOs, n=19), and oxygen group (GO2, n=18). The model was induced by single intraperitoneal injection of STZ. Ozone or oxygen enteroclysm was given twice per week for 4wk. F-ERG and histopathological examinations were performed one month after treatment. RESULTS: Under dark adaption, as compared to GB, the other groups each had differential decreases in the a-wave amplitudes (P〈0.05); the latencies were delayed in GM, GO2, and GO3 rats (P〈0.05). Similar results were observed under light adaption, with the exception that the a-wave of the amplitudes (F=0.28, P〉0.05). There were significant differences in the apoptosis index among the groups (P〈0.05). Under ozone treatment, apoptosis was decreased in GO3 as compared to GM and GO2 . CONCLUSION: Ozone administration alleviates nerve damage and reduces pathology and apoptosis in the retinas of diabetic rats.展开更多
BACKGROUND Liraglutide is a glucagon-like peptide 1 receptor agonist analog that has been found to have a therapeutic effect in diabetes.In addition to its ability to treat diabetes,liraglutide has beneficial effects ...BACKGROUND Liraglutide is a glucagon-like peptide 1 receptor agonist analog that has been found to have a therapeutic effect in diabetes.In addition to its ability to treat diabetes,liraglutide has beneficial effects on the cardiovascular system and kidney as well as other beneficial effects,but its specific mechanism is not clear.In this study,a rat model of type 2 diabetes was established by administration of a high-sugar,high-fat diet combined with low-dose streptozotocin(STZ)to observe the effect of liraglutide on the kidneys of type 2 diabetes rats and the possible underlying mechanisms.AIM To explore whether liraglutide has a protective effect on type 2 diabetic rat kidneys and the underlying mechanisms.METHODS Eight-week-old male Sprague-Dawley rats were randomly divided into a control group,model group,low-dose liraglutide group,and high-dose liraglutide group.Control rats were fed a standard diet,while model group and intervention group rats were fed high-sugar,high-fat feed for 1 mo and then intraperitoneally injected with 40 mg/kg STZ to induce type 2 diabetes.The low-dose and highdose intervention groups received 100μg/kg and 200μg/kg liraglutide,respectively,once daily by subcutaneous injection.The control and model groups were given an equivalent volume of physiological saline for 8 wk.Pathological changes in renal tissues were observed by hematoxylin and eosin staining and periodic acid-Schiff staining,and GRP78 and caspase-12 expression was detected by Western blot and reverse transcription-polymerase chain reaction(RT-PCR).RESULTS Western blot analysis showed that GRP78 and caspase-12 protein expression in kidney tissue was significantly higher in model rats than in normal rats and lowerin the liraglutide-treated groups than in the model group,with a more significant decrease being observed in the high-dose group than in the low-dose group.RTPCR showed that the mRNA expression of GRP78 and caspase-12 was higher in model rats than in control rats and lower in the liraglutide-treated groups than in the model group,with the high-dose group exhibiting a more significant decrease than the low-dose group.CONCLUSION Liraglutide may delay the progression of diabetic nephropathy by reducing endoplasmic reticulum stress and protect the kidneys in a dose-dependent manner.展开更多
Objective:To investigate the antidiabetic,hypolipidaemic activities and histopathological changes ofIcacina trichantha(I.trichantha)tuber extract in alloxan induced diabetic rats.Methods:In the present study,80%methan...Objective:To investigate the antidiabetic,hypolipidaemic activities and histopathological changes ofIcacina trichantha(I.trichantha)tuber extract in alloxan induced diabetic rats.Methods:In the present study,80%methanol extract of I.trichanthatuber was tested on alloxan induced diabetic rats.They were randomly grouped into control(distilled water and glibenclamide)and experimental(200,400 and 600 mg/kg body weight).Diabetes was induced by a single intraperitoneal injection of 160 mg/kg body weight of alloxan.Blood glucose levels weremeasured using blood glucose test strips with AccuCheck Advantage II glucometer at 1,3,6,and 24 h on the first day and 1 h after treatment on Day 7,14 and 21.Blood samples were collected and centrifuged to separate serum for estimation of lipid profile and other biochemical parameters.Histopathological changes in diabetic rats pancreas were also studied after extract treatment.Results:Daily oral administration ofI.trichanthatuber extract(200,400,and 600 mg/kg bodyweight)and glibenclamide(2 mg/kg)showed beneficial effects on blood glucose level(P<0.01)as well as improving liver,kidney functions and hyperlipidaemia due to diabetes.The extract had a favourable effect on the histopathological changes of the pancreas in alloxan induced diabetes.Conclusions:I.trichanthatuber extracts posses antidiabetic activities as well as improve liver and renal profile and total lipids levels.I.trichanthatuber extracts also have favourable effects to inhibit the histopathological changes of the pancreas in alloxan induced diabetes.展开更多
文摘Background:Cucurbita maxima plant materials are frequently used to manage a number of disorders,according to previous studies.Objective:The goal of the present report was to look into further possible effects of this plant on kidney disorder in rats brought on by diabetes as well as the related abnormalities in lipid metabolism.Methods:To assess the ameliorative effect of the plant,streptozotocin(STZ)(45 mg/kg/day)was given as a single dosage to cause type 1 diabetes.After then,diabetic rats received supplemented diets of Cucurbita maxima for four weeks at 5%,10%,15%and 20%ad libidium.However,in another experiment to evaluate the preventive capacity of Cucurbita maxima,the STZ-induction came at the end of four weeks supplementation.Blood and kidney tissues were obtained at the end of the treatments and investigated.Consequently,the analysis of kidney function and lipid profile was made using serum obtained from the blood sample.Histological change in kidney was also observed using haematoxylin and eosin stain Results:Our findings demonstrated that Cucurbita maxima drastically(P<0.05)decreased the elevated kidney indicators such as urea and creatinine in the blood,and restored the electrolytes and lipid profiles anomalies as compared to the normal control.However,the alteration of biochemical parameters in the STZ-induced diabetic control remained unchanged throughout as compared to the normal control.The above mentioned biochemical changes that took place in kidney tissues were further corroborated by histological alterations.Conclusion:The results suggest that Cucurbita maxima leaves supplemented diets reversed STZ-induced renal disorder and abnormal lipid metabolism,and that these effects may be mediated by interacting with multiple receptors to raise the levels of antioxidant enzymes in the system.
基金Supported by grant from Fundamental Research Grant Scheme by Ministry of Higher Education(MoHE)600-IRMI/FRGS 5/3(101/2019).
文摘AIM:To investigate the stability of the seven housekeeping genes:beta-actin(ActB),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),18s ribosomal unit 5(18s),cyclophilin A(CycA),hypoxanthine-guanine phosphoribosyl transferase(HPRT),ribosomal protein large P0(36B4)and terminal uridylyl transferase 1(U6)in the diabetic retinal tissue of rat model.METHODS:The expression of these seven genes in rat retinal tissues was determined using real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)in two groups;normal control rats and streptozotocininduced diabetic rats.The stability analysis of gene expression was investigated using geNorm,NormFinder,BestKeeper,and comparative delta-Ct(ΔCt)algorithms.RESULTS:The 36B4 gene was stably expressed in the retinal tissues of normal control animals;however,it was less stable in diabetic retinas.The 18s gene was expressed consistently in both normal control and diabetic rats’retinal tissue.That this gene was the best reference for data normalisation in RT-qPCR studies that used the retinal tissue of streptozotocin-induced diabetic rats.Furthermore,there was no ideal gene stably expressed for use in all experimental settings.CONCLUSION:Identifying relevant genes is a need for achieving RT-qPCR validity and reliability and must be appropriately achieved based on a specific experimental setting.
基金Supported by Shanxi Provincial Natural Science Foundation,No.201701D121159Shanxi Provincial Health and Family Planning Commission,No.2014016Health Commission of Shanxi Province,No.2019020.
文摘BACKGROUND In recent years,studies have found that the occurrence and development of diabetic cardiomyopathy(DCM)is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1(PARP-1)activity.PARP-1 activation could be involved in the pathophysiological process of DCM by promoting oxidative stress,the inflammatory response,apoptosis and myocardial fibrosis.AIM To investigate the mechanism of liraglutide in improving myocardial injury in type 2 diabetic rats,further clarified the protective effect of liraglutide on the heart,and provided a new option for the treatment of DCM.METHODS Forty healthy male SD rats aged 6 wk were randomly divided into two groups,a normal control group(n=10)and a model group(n=30),which were fed an ordinary diet and a high-sugar and high-fat diet,respectively.After successful modeling,the rats in the model group were fed a high-glucose and high-fat diet for 4 wk and randomly divided into a model group and an intervention group(further divided into a high-dose group and a low-dose group).The rats were fed a high-glucose and high-fat diet for 8 wk and then started drug intervention.Blood samples were collected from the abdominal aorta to detect fasting blood glucose and lipid profiles.Intact heart tissue was dissected,and its weight was used to calculate the heart weight index.Haematoxylin and eosin staining was used to observe the pathological changes in the myocardium and the expression of PARP-1 in the heart by immunohistochemistry.RESULTS The body weight and heart weight index of rats in the model group were significantly increased compared with those in the normal control group,and those in the intervention group were decreased compared with those in the model group,with a more obvious decrease observed in the high-dose group(P<0.05).In the model group,myocardial fibers were disordered,and inflammatory cells and interstitial fibrosis were observed.The cardiomyopathy of rats in the intervention group was improved to different degrees,the myocardial fibers were arranged neatly,and the myocardial cells were clearly striated;the improvement was more obvious in the high-dose group.Compared with the normal control group,the expression of PARP-1 in myocardial tissue of the model group was increased,and the difference was statistically significant(P<0.05).After liraglutide intervention,compared with the model group,the expression of PARP-1 in myocardial tissue was decreased,and the reduction was more obvious in the high-dose group(P<0.05)but still higher than that in the normal control group.CONCLUSION Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial PARP-1 in a dose-dependent manner.
文摘AIM:To investigate the aldose reductase(AR)inhibition capacity of astragalin(AST)against streptozoticin-induced diabetic cataracts(DCs)in rats.METHODS:Ex vivo investigations were conducted by treating the lens of a goat placed for 72h in artificial aqueous humor(AAH)of pH 7.8 at room temperature with cataract-causing substance(55 mmol/L of galactose)and in vivo studies were performed on rats via induction with streptozotocin.AST was administered at different dose levels and scrutinize for DC activity.RESULTS:In diabetic rats,AST improved the body weight,blood insulin,and glucose as well as the levels of galactitol in a dose-dependent way,other biochemical parameters i.e.inflammatory mediators and cytokines,and also suppress AR activity.The level of the antioxidant parameters such as superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)activity were also altered on a diabetic lens after the administration of the AST.CONCLUSION:AST protects against lens opacification to avoid cataracts and polyols formation,indicating that it could be used as a potential therapeutic agent for diabetes.
文摘Objective: The present study consisted of challenging the extract of kombucha and the fungus Ganoderma reported as hypoglycemic and used as alternative treatments against diabetes on the number and morphology of islets of Langerhans. Material and Methods: 64 Wistar rats were used in 4 groups: one control, three experimental, streptozotocin, Kombucha y Ganoderma induced diabetes with streptozotocin. Divided into four post-induction stages at 2, 15, 30 and 45 days of treatment, sacrificing 4 rats at each stage, to perform the morphological analysis of the pancreas. Results: A decrease in the islets of Langerhans in size, volume and the number of cells within them was identified for the streptozotocin group from the second stage until almost disappearing due to diabetes, in the groups of Kombucha y Ganoderma the same was observed but they were recovered with the extract treatments and the average number of islets was similar in these groups, the group of Ganoderma. Conclusion: Under the conditions of this work, a protective and regenerative effect of both extracts is identified.
基金Supported by the National Natural Science Foundation in China(No.81671641)Jiangsu Provincial Medical Innovation Team(No.CXTDA2017039)Gusu Health Talents Program(No.GSWS 2022018).
文摘AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic condition.METHODS:The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells(HRMEC)under high glucose conditions was tested by a cell counting kit,wound healing,a transwell and a tube formation assay.The inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction(RT-PCR).The expression of the cell junction was measured by Western blotting(WB)and immunofluorescence staining.In addition,two groups of rat models,diabetic and non-diabetic,were fed with normal or 0.1%TMAO for 16wk,and their plasma levels of TMAO,vascular endothelial growth factor(VEGF),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere tested.The vascular permeability of rat retinas was measured using FITC-Dextran,and the expression of zonula occludens(ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence staining.RESULTS:TMAO administration significantly increased the cell proliferation,migration,and tube formation of primary HRMEC either in normal or high-glucose conditions.RT-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation,while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO treatment.Diabetic rats showed higher plasma levels of TMAO as well as retinal vascular leakage,which were even higher in TMAO-feeding diabetic rats.Furthermore,TMAO administration increased the rat plasma levels of VEGF,IL-6 and TNF-αwhile decreasing the retinal expression levels of ZO-1 and claudin-5.CONCLUSION:TMAO enhances the proliferation,migration,and tube formation of HRMEC,as well as destroys their vascular integrity and tight connection.It also regulates the expression of VEGF,IL-6,and TNF-α.
基金This research was supported by the Science Found of Zhejiang Province (No. 2004C32082)
文摘Objective To investigate the renal protective activity of Hsian-tsao Mesona procumbens Hemsl. water extracts in diabetic rats. Methods Thirty Sprague-dawley female rats were randomly divided into three groups (n=10 each), "control group" with intraperitoneal saline injection, "diabetic group" with 60 mg of intraperitoneal streptozotocin injection per kg of body weight and "Hsian-tsao group" with intragastric administration of Hsian-tsao extraction everyday for 4 weeks after intraperitoneal streptozotocin injection. The body weight and blood sugar were measured before and after model induction in the three groups. Thrombospondin-1 (TSP-1) expressions in the kidney were monitored by immunohistochemistry. Kidney ultrastructural changes were also analyzed by using transmission electron microscopy. Results Before diabetic model induction, there were no significant differences among the three groups in body weight and blood sugar. Four weeks after the induction of diabetes, the differences became statistically significant. Electron microscopy also revealed disruption of the foot processes of the podocytes and other damages in diabetic group. These damages were significantly less severe in Hsian-tsao group when compared with the diabetic group. TSP-1 expressions in the kidney were significantly increased in both the diabetic group and Hsian-tsao group, but it was relatively lower in Hsian-tsao group than in diabetic group. Conclusion Our results showed that Hsian-tsao treatment in the diabetic rats effectively prevented the pathological alterations in the kidney and decreased the TSP- 1 expression. It was suggested that Hsian-tsao had protective effect on the kidneys of the diabetic rats.
文摘Objective:To investigate the antidiabetic properties of aqueous extract of stem bark of Afzelia africana(A.africana)and its beneficial effect on haematological parameters in streptozotocin induced diabetic rats.Methods:A total of 30 rats including 24 diabetic and 6 normal rats were used for this study.Diabetes was induced in male Wistar rats by intraperitoneal injection of streptozotocin.After being confirmed diabetic,animals were orally treated with distilled water or extracts at 100 or 200 mg/kg body weight daily for 10 days.The haematological parameters including red blood and white blood cells and their functional indices were evaluated in diabetic treated groups compared with the controls.Results:The extract significantly reduced the blood glucose levels while the best result was obtained at 200 mg/kg body weight The feed and water intake in diabetic rats were significantly reduced while weight loss was minimized at both dosages.Similarly,the levels of red blood,white blood cells and their functional indices were significantly improved after extract administration at both doses.Conclusions:It can be concluded that the aqueous extract of bark of A.africana possesses antihyperglycemic properties.In addition,the extract can prevent various complications of diabetes and improve some haematological parameters.Further experimental investigation is needed to exploit its relevant therapeutic effect to substantiate its ethnomedicinal usage.
基金carried out through the funding Provided by CapePeninsula University of Technology,Bellville,South Africa(grant NO.NRF-CPUT/RJ24)
文摘Objective:To investigate the role of red palm oil(RPO),rooibos tea extract(RTE)and their combined treatment(RPO+RTE)on antioxidant status in streptozotocin(STZ)-induced diabetic rats.Methods:Diabetes mellitus was induced by a single administration of streptozotocin(50 mg/kg)and the rats were treated for 7 weeks.Antioxidant enzymes[calalase(CAT),glutathione peroxidase(GPx),superoxide dismutase(SOD)],antioxidant capacity[trolox equivalence antioxidant capacity(TEAC),oxygen radical absorbance capacity(ORAC)]as well as total protein,albumin,globulin,total glutathione,conjugated diene and thiobarbituric acid reactive substances(TBARS)were investigated.Results:Treatment with RPO,RTE and RPO+RTE significantly(p>0.05)improved liver SOD and plasma ORAC in the diabetic rats.Similarly,diabetic rats treated with RTE and RPO+RTE enhanced liver GPx.A significant(P<0.05)increase in the plasma TBARS in the diabetic control group was observed when compared with the normal control group.Treatment of diabetic rats with RTE and RPO+RTE reduced plasma TBARS to a level not significantly different at P<0.05 from the normal control group.Conclusions:The results revealed the anti-oxidative potentials of red palm oil,rooibos and their combination in diabetic conditions and hence,they could be useful in the management of diabetes and its complications.
基金Shahhag, Dhaka. Bangladesh, for providing technical moral ami financial support for this project
文摘Objective:To evaluate the antidiabetic and antioxidant potential of Emblica officinalis(E.officinalis)fruit on normal and type 2 diabetic rats.Methods:Type 2 diabetes was induced into the male Long-Evans rats.The rats were divided into nine groups including control groups receiving water,type 2 diabetic controls,type 2 diabetic rats treated with glibenclamide(T2GT)and type 2diabetic rats treated with aqueous extract of fruit pulp of E.officinalis.They were fed orally for8 weeks with a single feeding.Blood was collected by cutting the tail tip on 0 and 28 days and by decapitation on 56 day.Packed red blood cells and serum were used for evaluating different biochemical parameters.Results:Four weeks administration of aqueous extract of E.officinalis improved oral glucose tolerance in type 2 rats and after 8 weeks it caused significant(P<0.007)reduction in fasting serum glucose level compared to 0 day.Triglycerides decreased by 14%but there was no significant change in serum ALT,creatinine,cholesterol and insulin level in any group.Furthermore,reduced erythrocyte malondialdehyde level showed no significant change(P<0.07)but reduced glutathione content was found to be increased significantly(P<0.05).Conclusions:The aqueous extract of E.officinalis has a promising antidiabetic and antioxidant properties and may be considered for further clinical studies in drug development.
基金Supported by National Natural Science Foundation of China(No.81270999)the Key Project of Miaopu of Fujian Medical University(No.2015MP004)the Qihang Funds of Fujian Medical University(No.2018QH1063)
文摘AIM: To evaluate the effects of etanercept on the expression of Fas, tumor necrosis factor-alpha(TNF-α) and caspase-8 in the early stage of the apoptotic pathway in diabetic rats, and to explore the therapeutic effect of etanercept on diabetic retinopathy.METHODS: A total of 60 Sprague-Dawley(SD) rats were randomly and evenly divided into 3 groups with 20 rats each, including control group, and diabetic groups with or without treatment. Streptozotocin(STZ)-induced diabetic rats were established for diabetic groups. Blood glucose and body weight were measured weekly. All the rats were sacrificed at the 12 wk after treatment. The expressions of Fas, TNF-α and caspase-8 in rat retina were quantitatively detected by PCR and Western blot. The leakage of Evan blue was adopted to measure the retinal vascular leakage quantitatively, and to compare it among different groups. TUNEL method was used to compare the amount of apoptotic bodies quantitatively in rat retina ganglion cells under electron microscope.RESULTS: The expressions of Fas, TNF-α and caspase-8 in each group were compared via PCR and Western blot, in which the diabetic group with treatment was lower than those without treatment(P<0.01), but all the diabetic groups were higher than the control group(P<0.01). Evans blue leakage in the diabetic treatment group was lower than those without treatment(P<0.01), but those in the control group was the lowest compared with the other two groups(P<0.01). TUNEL method showed that the apoptoticbodies of retina in the diabetic treatment group was lower than those without treatment(P<0.01), while those in the control group was the lowest compared with the other two groups(P<0.01). CONCLUSION: Etanercept can effectively reduce the expression of Fas, TNF-α and caspase-8, as well as the retinal leakage and retinal cell apoptosis in diabetic rats.
文摘An Otsuka Long-Evans Tokushima Fatty(OLETF)rat provides a useful model for studies to develop corneal wound healing drugs for use in diabetic keratopathy resulting from type 2 diabetes mellitus.We investigated the effects of sericin on corneal wound healing in OLETF rats.Corneal wounds were prepared by removal of the corneal epithelium and documented using a TRC-50X.Sericin was instilled into the eyes of rats five times a day following corneal abrasion.The plasma levels of glucose,triglycerides,cholesterol and insulin in 38 wk old OLETF rats were significantly higher than in normal control rats(LETO rats),and the rate of corneal wound healing in OLETF rats was slower than in normal rat,probably due to the suppression of cell migration and proliferation caused by high plasma glucose levels.The corneal wounds of OLETF rats instilled with saline showed almost complete healing 72h after corneal epithelial abrasion.On the other hand,the instillation of sericin has a potent effect in promoting wound healing and wound size reduction in OLETF rats and the wounds showed almost complete healing at 48 h after abrasion.The sericin may be an effective and safe drug to promote corneal wound healing in diabetic keratopathy.
基金Supported by National Natural Science Fundation of China (No.81303282)Central Finance of China in Support of the Development of Local Colleges and University [Educational Finance Grant No.338 (2013/2014)]+1 种基金Department of Education of Guangdong Province (No.Yq2013044)Science and Information Technology of Guangzhou (No.2013J2200034)
文摘AIM: To evaluate effects of Danhong Huayu Koufuye (DHK, a Chinese medicinal formulae) alone or combined with metformin on diabetic retinopathy (DR) in Zucker diabetic fatty (ZDF) rats, an animal model of obese type -2 diabetes, and then to investigate the mechanisms. METHODS: ZDF (fa/fa) rats were administered with vehicle (distilled water), metformin, DHK, and DHK plus metformin. Electrophysiological and histological analysis were applied to evaluated effects of DHK alone or combined with metformin on DR. The levels of fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) in blood were measured to evaluate the antihyperglycemic activity of DHK. Furthermore, levels of nitric oxide (NO), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum were measured to study effects of DHK on oxidative stress in ZDF rats. In addition, body weight, lipidic indexes and insulin level were also assessed. RESULTS: DHK combined with metformin significantly reversed the prolongation of latency times of flash electroretinogram (FERG) and oscillatory potentials (OPs) in diabetic rats. Furthermore, DHK alone or combined with metformin showed a remarkable suppression of retinal neovascularization and amelioration of retinal internal limiting membrane morphology. Moreover, DHK alone or plus metformin reduced FBG (P<0.05), HbA1c 1094 (P<0.01) and MDA (P<0.01) levels in diabetic rats. In addition, reductions in levels of triglycerides (TG) (P<0.01) and low density lipoprotein cholesterol (LDL-c) (P<0.01 and P<0.05, respectively) were also observed in diabetic rats treated with DHK alone or plus metformin. CONCLUSION: DHK in combination with metformin had a preventive and therapeutic effect on DR in type-2 diabetic rats, and the possible mechanisms may be alleviating hyperglycemia, reducing oxidative stress and improving lipid metabolism.
文摘AIM: To evaluate the effect of β-elemene on the expressions of hypoxia-inducible factor(HIF)-lα, vascular endothelial growth factor(VEGF) and inducible nitric oxide synthase(i NOS) in a streptozotocin(STZ) induced diabetic SpragueDawley(SD) rat model.METHODS: SD rats were administered an abdominal injection of STZ and induced to a diabetic model. After 6 wk course of diabetes, the treatment groups were given β-elemene through periocular and intravitreous injection separately and the control groups were given blank emulsion injection. HE staining was used to observe the morphology of retina. The m RNA expressions of HIF-1α, VEGF and i NOS was assayed by real-time polymerase chain reaction(PCR) and the protein expression was measured by Western blot and immunocytochemistry methods.RESULTS: The results indicated that the protein and m RNA expressions of HIF-1α, VEGF and i NOS after treated by β-elemene periocularly and intravitreally injections were all found to be reduced compared with the levels in the diabetic rats group(P<0.05). The inhibitory effect of intravitreal injection was more remarkable.CONCLUSION: The results show β-elemene protect the retina of diabetic rats from high glucose damage by downregulating the expression of HIF-1α, VEGF and iNOS.
基金Supported by Biomedical Research Institute Grant(PNU-2013-0373),Pusan National University Hospital
文摘AIM: To investigate the effect of angiotensin II type 1 receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS: Forty Sprague-Dawley rats were divided into 4 groups: control, diabetes mellitus (DM), candesartan- treated DM, and enalapril-treated DM (each group, n---10). After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/(kg · d)] and enalapril [ACEI, 10 mg/(kg · d)] were administered to rats orally for 4Wko Vascular endothelial growth factor (VEGF) and angiotensin II (Ang II) concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor (ATIR) levels were assessed at week 4 by Western blotting. RESULTS: Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control (P=0.04 and 0.005, respectively). Vitreous ATIR increased significantly in DM compared to the other three groups (P〈0.007). Candesartan-treated DM rats showed higher vitreal ATIR concentration than the enalapril-treated DM group and control (P〈0.001 and P=0.005, respectively). No difference in vitreous Ang II and ATIR concentration was found between the enalapril- treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION: Increased Ang II and ATIR in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.
文摘AIM:To generate phasic and tonic stress-strain curves for evaluation of intestinal smooth muscle function in type 2 diabetic rats during active and passive conditions.METHODS:Seven diabetic Goto-Kakizaki(GK)male rats,32-wk old(GK group),and 9 age-matched normal Wistar rats(Normal group)were included in the study.Jejunal segments were distended up to a pressure of10 cm H2O in an organ bath containing 37℃Krebs solution with addition of carbachol(CA).The pressure and outer diameter changes were synchronously recorded.Passive conditions were obtained using calcium-free Krebs solution containing ethylene glycol tetraacetic acid and papaverine.Total phasic,tonic and passive circumferential stress and strain were computed from the diameter and pressure data with reference to the zero-stress state geometry.The active phasic and tonic stresses were defined as the total phasic and tonic stresses minus the passive stress.RESULTS:Diabetes increased jejunal mucosa and muscle layer thicknesses compared to the Normal group(mucosa,755.8±63.3 vs 633.1±59.1μm,P<0.01;muscle,106.3±12.9 vs 85.2±11.7μm,P<0.05).The pressure and stress thresholds were decreased in the GK group after CA application compared to distensions without CA application(pressure,1.01±0.07vs 1.99±0.19 cmH2O,P<0.01;stress,0.11±0.01vs 0.24±0.02 kPa,P<0.01).CA application did not change the pressure and stress threshold in the Normal group(pressure,2.13±0.32 vs 2.34±0.32 cm H2O,P>0.05;stress,0.25±0.03 vs 0.35±0.06 kPa,P>0.05).The amplitude of total phasic,total tonic,active phasic and active tonic circumferential stresses did not differ for the distensions without CA application between the GK group and the Normal group.However,the total phasic and total tonic stresses increased after CA application in the GK group compared those in the Normal group.When normalized to muscle layer thickness,the amplitude of active stresses before CA application was lowest in the GK group compared with the Normal group.No difference was found during CA application.CONCLUSION:The stress generated by intestinal muscle normalized to the muscle layer thickness was lowest in GK rats compared to normal rats whereas the response to CA stimulation was preserved.
文摘Objective:To investigate the hypoglycemic effect of the aqueous extract of Octomeles sumatrana (O.sumatrana)(OS) in streptozotocin-induced diabetic rats(STZ) and its molecular mechanisms. Methods:Diabetes was induced by intraperitoneal(i.p.) injection of streptozotocin(55 mg/kg) in to male Sprague-Dawley rats.Rats were divided into six different groups;normal control rats were not induced with STZ and served as reference,STZ diabetic control rats were given normal saline.Three groups were treated with OS aqueous extract at 0.2,0.3 and 0.5 g/kg,orally twice daily continuously for 21 d.The fifth group was treated with glibenclamide(6 mg/kg) in aqueous solution orally continuously for 21 d.After completion of the treatment period,biochemical parameters and expression levels of glucose transporter 2(Slc2a2),glucose-6-phosphatase (GoPase) and phosphoenolpyruvate carboxykinase(PCK1) were determined in liver by quantitative real time PCR.Results:Administration of OS at different doses to STZ induced diabetic rats, resulted in significant decrease(P【0.05) in blood glucose level in a dose dependent manner by 36%,48%,and 64%at doses of 0.2,0.3 and 0.5 g/kg,respectively,in comparison to the STZ control values.Treatment with OS elicited an increase in the expression level of Slc2a2 gene but reduced the expression of G6Pase and PCK1 genes.Morefore,OS treated rats,showed significantly lower levels of serum alanine transaminase(ALT),aspartate aminotransferase(AST) and urea levels compared to STZ untreated rats.The extract at different doses elicited signs of recovery in body weight gain when compared to STZ diabetic controls although food and water consumption were significantly lower in treated groups compared to STZ diabetic control group.Conclusions:O.sumatrana aqueous extract is beneficial for improvement of hyperglycemia by increasing gene expression of liver Slc2a2 and reducing expression of G6Pase and PCK1 genes in streptozotocin-induced diabetic rats.
基金Supported by the Xinjiang Natural Science Research Fund (No. 2014211C046)
文摘AIM: To study the histopathological changes in the retina and flash electroretinogram (F-ERG) features of ozone-treated streptozotocin (STZ)-induced diabetic rats. METHODS: Seventy male Sprague Dawley rats were grouped as follows: blank group (GB, n=10), model control group (GM, n=18), ozone group (GOs, n=19), and oxygen group (GO2, n=18). The model was induced by single intraperitoneal injection of STZ. Ozone or oxygen enteroclysm was given twice per week for 4wk. F-ERG and histopathological examinations were performed one month after treatment. RESULTS: Under dark adaption, as compared to GB, the other groups each had differential decreases in the a-wave amplitudes (P〈0.05); the latencies were delayed in GM, GO2, and GO3 rats (P〈0.05). Similar results were observed under light adaption, with the exception that the a-wave of the amplitudes (F=0.28, P〉0.05). There were significant differences in the apoptosis index among the groups (P〈0.05). Under ozone treatment, apoptosis was decreased in GO3 as compared to GM and GO2 . CONCLUSION: Ozone administration alleviates nerve damage and reduces pathology and apoptosis in the retinas of diabetic rats.
文摘BACKGROUND Liraglutide is a glucagon-like peptide 1 receptor agonist analog that has been found to have a therapeutic effect in diabetes.In addition to its ability to treat diabetes,liraglutide has beneficial effects on the cardiovascular system and kidney as well as other beneficial effects,but its specific mechanism is not clear.In this study,a rat model of type 2 diabetes was established by administration of a high-sugar,high-fat diet combined with low-dose streptozotocin(STZ)to observe the effect of liraglutide on the kidneys of type 2 diabetes rats and the possible underlying mechanisms.AIM To explore whether liraglutide has a protective effect on type 2 diabetic rat kidneys and the underlying mechanisms.METHODS Eight-week-old male Sprague-Dawley rats were randomly divided into a control group,model group,low-dose liraglutide group,and high-dose liraglutide group.Control rats were fed a standard diet,while model group and intervention group rats were fed high-sugar,high-fat feed for 1 mo and then intraperitoneally injected with 40 mg/kg STZ to induce type 2 diabetes.The low-dose and highdose intervention groups received 100μg/kg and 200μg/kg liraglutide,respectively,once daily by subcutaneous injection.The control and model groups were given an equivalent volume of physiological saline for 8 wk.Pathological changes in renal tissues were observed by hematoxylin and eosin staining and periodic acid-Schiff staining,and GRP78 and caspase-12 expression was detected by Western blot and reverse transcription-polymerase chain reaction(RT-PCR).RESULTS Western blot analysis showed that GRP78 and caspase-12 protein expression in kidney tissue was significantly higher in model rats than in normal rats and lowerin the liraglutide-treated groups than in the model group,with a more significant decrease being observed in the high-dose group than in the low-dose group.RTPCR showed that the mRNA expression of GRP78 and caspase-12 was higher in model rats than in control rats and lower in the liraglutide-treated groups than in the model group,with the high-dose group exhibiting a more significant decrease than the low-dose group.CONCLUSION Liraglutide may delay the progression of diabetic nephropathy by reducing endoplasmic reticulum stress and protect the kidneys in a dose-dependent manner.
基金Financially supported by the Institute of International Education (IIE)of the United States Department of State’s Bureau for Educational and Cultural Affairs(Grant No.15120356)
文摘Objective:To investigate the antidiabetic,hypolipidaemic activities and histopathological changes ofIcacina trichantha(I.trichantha)tuber extract in alloxan induced diabetic rats.Methods:In the present study,80%methanol extract of I.trichanthatuber was tested on alloxan induced diabetic rats.They were randomly grouped into control(distilled water and glibenclamide)and experimental(200,400 and 600 mg/kg body weight).Diabetes was induced by a single intraperitoneal injection of 160 mg/kg body weight of alloxan.Blood glucose levels weremeasured using blood glucose test strips with AccuCheck Advantage II glucometer at 1,3,6,and 24 h on the first day and 1 h after treatment on Day 7,14 and 21.Blood samples were collected and centrifuged to separate serum for estimation of lipid profile and other biochemical parameters.Histopathological changes in diabetic rats pancreas were also studied after extract treatment.Results:Daily oral administration ofI.trichanthatuber extract(200,400,and 600 mg/kg bodyweight)and glibenclamide(2 mg/kg)showed beneficial effects on blood glucose level(P<0.01)as well as improving liver,kidney functions and hyperlipidaemia due to diabetes.The extract had a favourable effect on the histopathological changes of the pancreas in alloxan induced diabetes.Conclusions:I.trichanthatuber extracts posses antidiabetic activities as well as improve liver and renal profile and total lipids levels.I.trichanthatuber extracts also have favourable effects to inhibit the histopathological changes of the pancreas in alloxan induced diabetes.