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Triolein emulsion infusion into the hepatic artery increases vascular permeability to doxorubicin in rabbit liver
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作者 Yong-Woo Kim Hak Jin Kim +1 位作者 Byung Mann Cho Seon Hee Choi 《World Journal of Gastroenterology》 SCIE CAS 2021年第2期152-161,共10页
BACKGROUND The infusion of triolein emulsion(TE)induced increased vascular permeability and a negligible and temporary decrease in liver function without specific histopathological damage.AIM To assess changes in doxo... BACKGROUND The infusion of triolein emulsion(TE)induced increased vascular permeability and a negligible and temporary decrease in liver function without specific histopathological damage.AIM To assess changes in doxorubicin concentration according to the percentage of TE infused via a hepatic artery to study the vascular permeability in the rabbit liver.METHODS Thirty-nine healthy rabbits were divided into five groups according to the concentration of emulsified triolein infused into the hepatic arteries:Group 0,saline infusion(control group,n=5);group 1,0.3%TE(n=13);group 2,0.6%TE(n=6);group 3,0.9%TE(n=8);and group 4,1.5%TE(n=6).Doxorubicin(2.4 mg/kg)was infused immediately after TE injection via the hepatic arteries.After 2 h,the livers were harvested,and doxorubicin concentrations were calculated fluorometrically.The doxorubicin concentrations were compared between TE groups and the control group,and the optimal concentrations within the TE groups were calculated.Statistical analysis was performed using the nonparametric Mann-Whitney U test and Kruskal-Wallis test.P<0.05 were considered statistically significant.RESULTS In the liver,doxorubicin concentrations were 2.06,2.07,2.16 and 1.66 times higher in groups 1 through 4,respectively,and significantly higher in the TE groups than in the control group(all P<0.05).However,there were no significant differences in the mean doxorubicin concentrations between the four TE groups(P=0.642).In the lungs,the mean doxorubicin concentrations were not significantly different between the control and TE groups(P>0.05).CONCLUSION TE infusion into the hepatic arteries significantly increased the doxorubicin concentration approximately twofold but was not different between the TE groups.These findings suggest that TE infusion might be a useful adjuvant treatment of liver cancers. 展开更多
关键词 Triolein emulsion Liver tumor CHEMOTHERAPY Drug delivery vascular permeability Dexorubicin
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AB039. BMP9 signaling maintains endothelial integrity and prevents hyperglycemia-induced retinal vascular permeability
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作者 Naoufal Akla Claire Viallard +3 位作者 Natalija Popovic Cindy Lora Gil Przemyslaw Sapieha Bruno Larrivée 《Annals of Eye Science》 2019年第1期214-214,共1页
Background:The maintenance of a quiescent retinal vascular endothelial barrier is paramount for tissue supply and homeostasis to ensure visual function.Chronic hyperglycemia in diabetes causes structural and functiona... Background:The maintenance of a quiescent retinal vascular endothelial barrier is paramount for tissue supply and homeostasis to ensure visual function.Chronic hyperglycemia in diabetes causes structural and functional alterations of the endothelium that are accelerated by the production of several mediators such as VEGF.The disturbance of interendothelial junction stability leading to retinal hyperpermeability is one of the changes leading to diabetic macular edema(DME)that can occur at any stage of diabetic retinopathy.Advances in our understanding of the pathophysiological mechanisms of DME have enabled effective new therapies such as anti-VEGF’s,which are however associated with non-negligible side effects.The discovery of endothelium-specific protective targets that could restore retinal endothelial quiescence could provide a therapeutic alternative.Signaling mediated by BMP9 circulating protein via its endothelium-specific receptor ALK1,is known for its role in the maintenance of vascular quiescence.However,its ability to protect the endothelium and prevent vascular permeability has not been tested in the context of diabetes.Methods:We investigated BMP9/ALK1 signalling pathway in the hyperglycemic endothelium and its effect on retinal permeability in a type 1 diabetes mouse model.Hyperglycemic endothelial cells and tissue were extracted to evaluate BMP9/ALK1 signaling.BMP9 overexpression was achieved using adenoviral vectors.Retinal permeability was measured using miles assay.Results:We found that BMP9/ALK1 signaling was inhibited in hyperglycemic endothelial cells and blood vessels of diabetic(DB)mice,and that this loss of function was directly associated with retinal hyperpermeability.Molecularly,inhibition of this pathway triggers the activation of the VEGFR2/SRC pathway reducing interendothelial adhesion junctions.Conversely,the activation of ALK1 by sustained BMP9 overexpression in DB mice enabled the restoration of physiological permeability by regulating the levels and localization of interendothelial junctions,in part by limiting the action of VEGF signalling.We also observed that BMP9 overexpression demonstrated a regulating effect of blood glucose levels in DB mice.Our results showed that BMP9 significantly ameliorates glucose control over a 4-week span in DB mice and that this regulation was mediated primarily via the ALK3 receptor inhibiting gluconeogenic gene expression and hepatic glucose production and hence hyperglycemia.Conclusions:Together,our data show that BMP9 acts on several levels to safeguard endothelial integrity preventing retinal hyperpermeability in DB mice.The effects are mediated by its endocrine effect by directly stabilizing the endothelial barrier through Alk1 and its hypoglycemic paracrine/autocrine action in the liver through Alk3.Thus,BMP9 could be used in the development of future therapeutic alternatives against several vascular diseases involving edematous complications. 展开更多
关键词 DIABETES vascular permeability activin receptor
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AB004. Regulation of retinal angiogenesis and vascular permeability by bone morphogenetic protein signaling
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作者 Bruno Larrivée 《Annals of Eye Science》 2018年第1期410-410,共1页
The bone morphogenetic protein(BMP)family of proteins has a multitude of roles throughout the body.It plays important roles in development and in the adult vascular endothelium,by modulating the angiogenic response.Th... The bone morphogenetic protein(BMP)family of proteins has a multitude of roles throughout the body.It plays important roles in development and in the adult vascular endothelium,by modulating the angiogenic response.The endothelial-specific receptor BMP receptor Alk1 is of particular importance in the proper remodeling of the vasculature and its ligand BMP9 has been shown to be a potent inhibitor of neovascularization.Dysregulated BMP signaling has been linked to multiple vascular diseases and can lead to the abnormal angiogenesis.We therefore investigated the role of BMP9/Alk1 signaling in retinal angiogenesis,and its therapeutic implications for vascular pathologies of the eye. 展开更多
关键词 Retinal angiogenesis bone morphogenetic protein(BMP) vascular permeability
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Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function:implication of miRNAs and microvesicles
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作者 Zi-Sen Zhang Yi-Yan Liu +10 位作者 Shuang-Shuang He Dai-Qin Bao Hong-Chen Wang Jie Zhang Xiao-Yong Peng Jia-Tao Zang Yu Zhu Yue Wu Qing-Hui Li Tao Li Liang-Ming Liu 《Military Medical Research》 SCIE CAS CSCD 2024年第1期1-18,共18页
Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity... Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and permeability.Methods We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)challenge.In a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive days.Cultured pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic investigations.The effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also examined.Results CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.Conclusions Pericytes are protective against sepsis through regulating vascular reactivity and barrier function.Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs. 展开更多
关键词 PERICYTE vascular reactivity vascular permeability CX43 MICROVESICLE
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Knockdown of fibrillin-1 suppresses retina-blood barrier dysfunction by inhibiting vascular endothelial apoptosis under diabetic conditions
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作者 Yue Zhang Xiao-Jing Liu +8 位作者 Xin-Ran Zhai Yao Yao Bin Shao Yu-Han Zhen Xin Zhang Zhe Xiao Li-Fang Wang Ming-Lian Zhang Zhi-Min Chen 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第8期1403-1410,共8页
AIM:To investigate the effects of fibrillin-1(FBN1)deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic conditions.METHODS:Streptozotocin(STZ)-induc... AIM:To investigate the effects of fibrillin-1(FBN1)deletion on the integrity of retina-blood barrier function and the apoptosis of vascular endothelial cells under diabetic conditions.METHODS:Streptozotocin(STZ)-induced diabetic mice were used to simulate the diabetic conditions of diabetic retinopathy(DR)patients,and FBN1 expression was detected in retinas from STZ-diabetic mice and controls.In the Gene Expression Omnibus(GEO)database,the GSE60436 dataset was selected to analyze FBN1 expressions in fibrovascular membranes from DR patients.Using lentivirus to knock down FBN1 levels,vascular leakage and endothelial barrier integrity were detected by Evans blue vascular permeability assay,fluorescein fundus angiography(FFA)and immunofluorescence labeled with tight junction marker in vivo.High glucose-induced monkey retinal vascular endothelial cells(RF/6A)were used to investigate effects of FBN1 on the cells in vitro.The vascular endothelial barrier integrity and apoptosis were detected by trans-endothelial electrical resistance(TEER)assay and flow cytometry,respectively.RESULTS:FBN1 mRNA expression was increased in retinas of STZ-induced diabetic mice and fibrovascular membranes of DR patients(GSE60436 datasets)using RNA-seq approach.Besides,knocking down of FBN1 by lentivirus intravitreal injection significantly inhibited the vascular leakage compared to STZ-DR group by Evans blue vascular permeability assay and FFA detection.Expressions of tight junction markers in STZ-DR mouse retinas were lower than those in the control group,and knocking down of FBN1 increased the tight junction levels.In vitro,30 mmol/L glucose could significantly inhibit viability of RF/6A cells,and FBN1 mRNA expression was increased under 30 mmol/L glucose stimulation.Down-regulation of FBN1 reduced high glucose(HG)-stimulated retinal microvascular endothelial cell permeability,increased TEER,and inhibited RF/6A cell apoptosis in vitro.CONCLUSION:The expression level of FBN1 increases in retinas and vascular endothelial cells under diabetic conditions.Down-regulation of FBN1 protects the retina of early diabetic rats from retina-blood barrier damage,reduce vascular leakage,cell apoptosis,and maintain vascular endothelial cell barrier function. 展开更多
关键词 diabetic retinopathy fibrillin-1 retinablood barrier vascular leakage vascular permeability APOPTOSIS retinal vascular endothelial cells
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Fingolimod alters inflammatory mediators and vascular permeability in intracerebral hemorrhage 被引量:13
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作者 Yu-Jing Li Guo-Qiang Chang +6 位作者 Yuanchu Liu Ye Gong Chunsheng Yang Kristofer Wood Fu-Dong Shi Ying Fu Yaping Yan 《Neuroscience Bulletin》 SCIE CAS CSCD 2015年第6期755-762,共8页
Intracerebral hemorrhage (ICH) leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated tha... Intracerebral hemorrhage (ICH) leads to high rates of death and disability. The pronounced inflammatory reactions that rapidly follow ICH contribute to disease progression. Our recent clinical trial demonstrated that oral administration of an immune modulator fingolimod restrained secondary injury derived from initial hematoma, but the mechanisms remain unknown. In this study, we aim to investigate the effects of fingolimod on inflammatory mediators and vascular permeability in the clinical trial of oral fingolimod for intracerebral hemorrhage (ICH). The results showed that fingolimod decreased the numbers of circulating CD4~ T, CD8~ T, CD19~ B, NK, and NKT cells and they recovered quickly after the drug' was stopped. The plasma ICAM level was decreased and IL-10 was increased by fingolimod. Interestingly, fingolimod protected vascular permeability as indicated by a decreased plasma level of MMP9 and the reduced rT1%. In conclusion, modulation of systemic inflammation by fingolimod demonstrates that it is an effective therapeutic agent for ICH. Fingolimod may prevent perihematomal edema enlargement by protecting vascular permeability. 展开更多
关键词 FINGOLIMOD inflammatory mediator vascular permeability intracerebral hemorrhage
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Regulatory mechanisms,prophylaxis and treatment of vascular leakage following severe trauma and shock 被引量:9
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作者 Chen-Yang Duan Jie Zhang +2 位作者 Hui-Ling Wu Tao Li Liang-Ming Liu 《Military Medical Research》 SCIE CAS 2017年第2期109-120,共12页
Vascular leakage, or increased vascular permeability, is a common but important pathological process for various critical diseases, including severe trauma, shock, sepsis, and multiple organ dysfunction syndrome(MODS)... Vascular leakage, or increased vascular permeability, is a common but important pathological process for various critical diseases, including severe trauma, shock, sepsis, and multiple organ dysfunction syndrome(MODS), and has become one of the most important causes of death for intensive care units(ICU) patients. Currently, although there has been some progress in knowledge of the pathogenesis of these vascular disorders, the detailed mechanisms remain unclear, and effective prophylaxis and treatment are still lacking. In this study, we aimed to provide a review of the literature regarding the regulatory mechanisms and prophylaxis as well as the treatment of vascular leakage in critical diseases such as severe trauma and shock, which could be beneficial for the overall clinical treatment of vascular leakage disorders. 展开更多
关键词 Clinical critical diseases vascular leakage vascular permeability Shock SEPSIS
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Effect of High Frequency Oscillatory Ventilation on EVLW and Lung Capillary Permeability of Piglets with Acute Respiratory Distress Syndrome Caused by Pulmonary and Extrapulmonary Insults 被引量:8
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作者 李秋杰 袁茵 +2 位作者 李玉梅 孙乐英 袁世荧 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2015年第1期93-98,共6页
The effect of high frequency oscillatory ventilation(HFOV) at early stage on hemodynamic parameters, extravascular lung water(EVLW), lung capillary permeability, CC16 and s ICAM-1 in piglets with pulmonary or extr... The effect of high frequency oscillatory ventilation(HFOV) at early stage on hemodynamic parameters, extravascular lung water(EVLW), lung capillary permeability, CC16 and s ICAM-1 in piglets with pulmonary or extrapulmonary acute respiratory distress syndrome(ARDS) was explored. Central vein pressure(CVP) and pulse indicator continuous cardiac output(Pi CCO) were monitored in 12 anesthetized and intubated healthy piglets. Pulmonary ARDS(ARDSp) and extrapulmonary ARDS(ARDSexp) models were respectively established by lung lavage of saline solution and intravenous injection of oleic acid. Then the piglets received HFOV for 4 h. EVLW index(EVLWI), EVLW/intratroracic blood volume(ITBV) and pulmonary vascular permeability index(PVPI) were measured before and after modeling(T0 and T1), and T2(1 h), T3(2 h), T4(3 h) and T5(4 h) after HFOV. CC16 and s ICAM-1 were also detected at T1 and T5. Results showed at T1, T3, T4 and T5, EVLWI was increased more significantly in ARDSp group than in ARDSexp group(P〈0.05). The EVLWI in ARDSp group was increased at T1(P=0.008), and sustained continuously within 2 h(P=0.679, P=0.216), but decreased at T4(P=0.007) and T5(P=0.037). The EVLWI in ARDSexp group was also increased at T1(P=0.003), but significantly decreased at T3(P=0.002) and T4(P=0.019). PVPI was increased after modeling in both two groups(P=0.004, P=0.012), but there was no significant change within 4 h(T5) under HFOV in ARDSp group, while PVPI showed the increasing trends at first, then decreased in ARDSexp group after HFOV. The changes of EVLW/ITBV were similar to those of PVPI. No significant differences were found in ΔEVLWI(P=0.13), ΔPVPI(P=0.28) and ΔEVLW/ITBV between the two groups(P=0.63). The significant decreases in both CC16 and s ICAM-1 were found in both two groups 4 h after HFOV, but there was no significant difference between the two groups. It was concluded that EVLWI and lung capillary permeability were markedly increased in ARDSp and ARDSexp groups. EVLW could be decreased 4 h after the HFOV treatment. HFOV, EVLW/ITBV and PVPI were increased slightly at first, and then decreased in ARDSexp group, while in ARDSp group no significant difference was found after modeling. No significant differences were found in the decreases in EVLW and lung capillary permeability 4 h after HFOV. 展开更多
关键词 acute respiratory distress syndrome high frequency oscillatory ventilation extravascular lung water lung vascular permeability index CC16 s ICAM-1
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Pretreatment with scutellaria baicalensis stem-leaf total flavonoid protects against cerebral ischemia/reperfusion injury in hippocampal neurons 被引量:7
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作者 Xiangyu Kong Wei Kong +4 位作者 Guangxin Miao Shumin Zhao Meng Chen Xiaoying Zheng Jiangtao Bai 《Neural Regeneration Research》 SCIE CAS CSCD 2014年第23期2066-2073,共8页
Previous experimental studies have shown that cerebral infarction can be effectively reduced following treatment with scutellaria baicalensis stem-leaf total flavonoid (SSTF). However, the mechanism of action of SST... Previous experimental studies have shown that cerebral infarction can be effectively reduced following treatment with scutellaria baicalensis stem-leaf total flavonoid (SSTF). However, the mechanism of action of SSTF as a preventive drug to treat cerebral infarction remains unclear. In this study, Sprague-Dawley rats were pretreated with 50, 100, 200 mg/kg SSTF via intragastric ad- ministration for 1 week prior to the establishment of focal cerebral ischemia/reperfusion injury. The results showed that pretreatment with SSTF effectively improved neurological function, reduced brain water content and the permeability of blood vessels, ameliorated ischemia-induced morphology changes in hippocampal microvessels, down-regulated Fas and FasL protein expression, elevated the activity of superoxide dismutase and glutathione peroxidase, and decreased malondialdehyde content. In contrast to low-dose SSTF pretreatment, the above changes were most obvious after pretreatment with moderateand high-doses of SSTF. Experimental findings indicate that SSTF pretreatment can exert protective effects on the brain against cerebral ischemia/reperfusion injury. The underlying mechanisms may involve reducing brain water content, increasing microvascular recanalization, inhibiting the apoptosis of hippocampal neurons, and attenuating free radical damage. 展开更多
关键词 nerve regeneration scutellaria baicalensis stem-leaf total flavonoid PRETREATMENT cerebral ischemia/reperfusion HIPPOCAMPUS apoptosis vascular permeability free radicals neural regeneration
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Protective effects of dl-3n-butylphthalide against diffuse brain injury 被引量:7
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作者 Yaning Zhao Jianmin Li +2 位作者 Pan Zhang Changxiang Chen Shuxing Li 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第28期2615-2624,共10页
DI-3n-butyiphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this... DI-3n-butyiphthalide can effectively treat cerebral ischemia; however, the mechanisms underlying the effects of dl-3n-butylphthalide on microcirculation disorders following diffuse brain injury remain unclear. In this study, models of diffuse brain injury were established in Sprague-Dawley rats with the vertical impact method. DI-3n-butylphthalide at 80 and 160 mg/kg was given via intraperitoneal injection immediately after diffuse brain injury. Ultrastructural changes in the cerebral cortex were observed using electron microscopy. Cerebral blood flow was measured by laser Doppler flowmetry, vascular density was marked by tannic acid-ferric chloride staining, vascular permeability was es- timated by the Evans blue method, brain water content was measured using the dry-wet method, and rat behavior was measured by motor function and sensory function tests. At 6, 24, 48, and 72 hours after administration of dl-3n-butylphthalide, reduced cerebral ultrastructure damage, in- creased vascular density and cerebral blood flow, and improved motor and sensory functions were observed. Our findings demonstrate that dl-3n-butylphthalide may have protective effects against diffuse brain injury by ameliorating microcirculation disorder and reducing blood-brain barrier dam- age and cerebral edema. 展开更多
关键词 neural regeneration brain injury diffuse brain injury blood-brain barrier brain edema vasculardensity cerebral blood flow vascular permeability brain water content grants-supported paper NEUROREGENERATION
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Naringin ameliorates acetic acid induced colitis through modulation of endogenous oxido-nitrosative balance and DNA damage in rats 被引量:8
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作者 Venkatashivam Shiva Kumar Anuchandra Ramchandra Rajmane +3 位作者 Mohammad Adil Amit Dattatraya Kandhare Pinaki Ghosh Subhash Laxman Bodhankar 《The Journal of Biomedical Research》 CAS 2014年第2期132-145,共14页
The aim of this study was to evaluate the effect of naringin on experimentally induced inflammatory bowel dis- ease in rats. Naringin (20, 40 and 80 mg/kg) was given orally for 7 days to Wistar rats before induction... The aim of this study was to evaluate the effect of naringin on experimentally induced inflammatory bowel dis- ease in rats. Naringin (20, 40 and 80 mg/kg) was given orally for 7 days to Wistar rats before induction of colitis by intrarectal instillation of 2 mL of 4% (v/v) acetic acid solution. The degree of colonic mucosal damage was analyzed by examining mucosal damage, ulcer area, ulcer index and stool consistency. Intrarectal administration of 4% acetic acid resulted in significant modulation of serum alkaline phosphatase, lactate dehydrogenase, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) content along with colonic nitric oxide (NO), xanthine oxidase (XO) level and protein carbonyl content in the colonic tissue as well as in blood. Naringin (40 and 80 mg/kg) exerted a dose dependent (P 〈 0.05) ameliorative effect, as it significantly increased hematological parameter as well as colonic SOD and GSH. There was a significant (P 〈 0.05) and dose dependant inhibition of macroscopical score, ulcer area along with colonic MDA, MPO activity by the 7 days of pretreatment of naringin (40 and 80 mg/kg). Biochemical studies revealed a significant (P 〈 0.05) dose dependant inhibition in serum alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels by pretreatment of naringin. Increased levels of colonic NO, XO, protein carbonyl content and DNA damage were also sig- nificantly decreased by naringin pretreatment. The findings of the present investigation propose that naringin has an anti-inflammatory, anti-oxidant and anti-apoptotic potential effect at colorectal sites as it modulates the production and expression of oxidative mediators such as MDA, MPO, NO and XO, thus reducing DNA damage. 展开更多
关键词 acetic acid apoptosis fluorimetric analysis of DNA unwinding inflammatory bowel disease my-eloperoxidase naringin nitrite/nitrate oxidative stress porotein carbonyl content vascular permeability xanthineoxidase
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Effect of Qinggan Huayu granule on H22 liver ascitic tumor mice
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作者 Fei-Ya Suo Xiao-Ran Zhu +1 位作者 Zhen-Huan Yang Shu-Kun Yao 《Journal of Hainan Medical University》 2022年第9期1-7,共7页
Objective:To evaluate the therapeutic effect of Qinggan Huayu granule on mice with H22 liver cancer ascites tumor.Methods:A H22 liver cancer ascites mouse model was established by intraperitoneally injecting H22 liver... Objective:To evaluate the therapeutic effect of Qinggan Huayu granule on mice with H22 liver cancer ascites tumor.Methods:A H22 liver cancer ascites mouse model was established by intraperitoneally injecting H22 liver cancer cells.Mice were randomly divided into the model group,the Ganfule group(1.35 g/kg),the fluorouracil group(50 mg/kg i.p),the Qinggan Huayu granule groups at low(0.67 g/kg),medium(1.34 g/kg),and high(2.68 g/kg)doses.Then the mice were administered continuously for 10 days and body weight and abdominal circumference were monitored every 3 days.On day 11,eight rats in each group were randomly selected for dissection to detect the amount of peritoneal water,peritoneal permeability and histopathological changes.The remaining mice were observed for survival.In addition,the vascular endothelial growth factor A(VEGFA)and vascular endothelial growth factor receptor 2(VEGFR2)were determined by Western blotting.Results:Compared with the model group,the weight growth of mice in the fluorouracil group and the medium-dose and high-dose Qinggan Huayu granule groups was slower(P<0.05).Moreover,the abdominal circumference of mice in each treatment group was increased slowly.There were significant differences in abdominal circumference between the fluorouracil group,the medium-dose group and the control group from day 6(P<0.05)while the abdominal circumference of the high dose group was significantly smaller than that of the control group from day 12(P<0.05).Moreover,compared with the model group,the amount of ascites in the medium-and high-dose Qinggan Huayu granule groups was decreased significantly(P<0.05).The optical density value of ascites supernatant in medium-and high-dose Qinggan Huayu granule group and the fluorouracil group decreased significantly(P<0.05)and the survival period of the medium-dose Qinggan Huayu granule group and the fluorouracil group was prolonged prominently(P<0.05).There was no significant difference in the low-dose Qinggan Huayu granule group and the Ganfule group.Peritoneal histopathological assay showed more complete peritoneal structure,less edema and less angiogenesis of the peritoneum in the fluorouracil group and the medium-and high-dose Qinggan Huayu granule group,which was better than that of the Ganfule group and the low-dose group.Compared with the model group,the expressions of VEGFA and VEGFR2 in the medium-dose Qinggan Huayu granule group decreased significantly(P<0.05,P<0.01).Conclusion:Qinggan Huayu granule can inhibit ascites production in the mice model with H22 liver cancer ascites tumor,prolong the survival of mice,and reduce peritoneal permeability and suppress the increase of peritoneal neovascularization.The mechanism may be related to the inhibition of VEGF/VEGFR pathway. 展开更多
关键词 H22 liver cancer ascites tumor Mouse Qinggan Huayu granule Survival period Peritoneal vascular permeability
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AB010.Promotion of BMP9/ALK1 quiescence signaling for the prevention of diabetic macular edema(DME)
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作者 Naoufal Akla Claire Viallard +2 位作者 Cindy Lora Gil Sapieha Przemyslaw Bruno Larrivée 《Annals of Eye Science》 2018年第1期416-416,共1页
Background:Sight-threatening diabetic macular edema(DME)is caused by increased microvascular permeability.While few direct vascular targeting strategies are available,VEGF pathway inhibition has shown to be effective ... Background:Sight-threatening diabetic macular edema(DME)is caused by increased microvascular permeability.While few direct vascular targeting strategies are available,VEGF pathway inhibition has shown to be effective in reducing retinal vascular leakage but is associated with non-negligible side effects.Thus,more options are needed.Vascular specific Activin-like kinase receptor type I(ALK1)pathway and its circulating ligand Bone morphogenetic protein-9(BMP9)is known for its potent quiescent and stabilizing effect on the vasculature.However,little is known about this pathway in the context of microvascular permeability associated with diabetes.We hypothesize that BMP9/ALK1 pathway is inhibited in diabetic(DB)retinas leading to vascular destabilization and leakage and that its activation could re-establish proper vascular endothelial barrier functions(EBF).Methods:The effect of hyperglycemia(i.e.,HG>10 mM of D-glucose)on Alk1 signaling was evaluated in vitro by subjecting endothelial cells(EC)to increasing concentrations of D-glucose(5,11,25 mM)and in vivo using DB mice(Streptozotocin-induced diabetes).The contribution of Alk1 signaling on EBF was evaluated using Evans Blue permeation in inducible endothelial specific Alk1 KO mice.To evaluate the potential protective effects of BMP9/Alk1 signaling on EBF,BMP9 overexpression was achieved using adenoviral delivery in DB mice.Statistical-One-Way ANOVA or Student’s t-test was used.Results:Endothelial tissue from DB mice showed a significant inhibition of BMP9/ALK1-canonical Smad1,5,8 quiescence signaling(DB n=5;CTL n=4;P<0.01),which was associated with reduced expression of target genes(JAG1,Id1,3,Hey1,2&HES).Moreover,we showed that retinal hyperpermeability associated with diabetes was exacerbated in Alk1 heterozygote mice(n=4-9/group;P<0.0001).Finally,we demonstrated that activation of Alk1 signaling in ECs prevented vascular permeability induced by HG,both in vitro(n=3;P=0.009)and in vivo(n=4-9/group;P<0.0001).Conclusions:Consistent with our hypothesis,vascular stability and quiescence induced by BMP9-ALK1 signaling is inhibited in the DB/HG endothelium which could be an important factor in vascular leakage leading to DME.Our results show that activation of this pathway could offer a therapeutically interesting future option to slow down the onset of DME. 展开更多
关键词 DIABETES RETINOPATHY diabetic macular edema(DME) vascular permeably
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Low-power Helium-Neon laser irradiation enhances the expression of VEGF in murine myocardium
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作者 张卫光 吴长燕 +2 位作者 潘文潇 田珑 夏家骝 《Chinese Medical Journal》 SCIE CAS CSCD 2004年第10期1476-1480,共5页
Background Low-power helium-neon (He-Ne) lasers have been increasingly widely applied in the treatment of cardiovascular diseases, and its vasodilation effect has been proven. The aim of this study was to determine t... Background Low-power helium-neon (He-Ne) lasers have been increasingly widely applied in the treatment of cardiovascular diseases, and its vasodilation effect has been proven. The aim of this study was to determine the effects of low-power He-Ne laser irradiation directed at the precardial region of Wistar rats on capillary permeability in the myocardium and the expression of myocardial vascular endothelial growth factor (VEGF). Methods Sixteen rats were divided randomly into control and irradiated groups (n=8, each). A He-Ne laser (632.8 nm) was applied to the irradiated group with a dose of 60.5 J/cm2. Ferritin was perfused into the left femoral vein and capillary permeability was examined under an electron microscope. VEGF expression in the myocardium was investigated by immunohistochemical methods, RT-PCR, and image analysis. Results The ultrastructures of the myocardial capillaries were examined. Compared to the control group, more high-density granules (ferritin), which were present within the capillary endothelium and the mitochondrions of myocardial cells in the internal layer of the myocardium, were observed in the irradiated group. VEGF staining of the myocardium was stronger in the irradiated group than that in the control group. The optic density of the irradiated group (0.246±0.015) was significantly higher than that of the control group (0.218±0.012, P<0.05). Finally, the levels of RT-PCR products of VEGF165 mRNA were 2.79 times higher in irradiated rats than in the control rats.Conclusions Our study demonstrates that He-Ne laser irradiation (in doses of 60.5 J/cm2) increases myocardial capillary permeability and the production of VEGF in myocardial microvessels and in myocardium. Our study provides experimental morphological evidence that myocardial microcirculation can be improved using He-Ne laser irradiation. 展开更多
关键词 vascular endothelial growth factor · capillary permeability ·He-Ne laser · heart
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