Objective This study aims to investigate the protection of procyanidins and lycopene from the renal damage induced by mercuric chloride.Methods Rats were treated with either procyanidins or lycopene 2h before HgCl 2 s...Objective This study aims to investigate the protection of procyanidins and lycopene from the renal damage induced by mercuric chloride.Methods Rats were treated with either procyanidins or lycopene 2h before HgCl 2 subcutaneously injection,once daily treatment for 2 successive days.Results In comparison with HgCl 2 group,markers of renal function such as blood urea nitrogen in serum and urinary protein were decreased to （18.45±11.63） mmol/L and （15.93±9.36） mmol/L,（4.54±0.78） g/（g Cr） and （4.40±1.12） g/（g Cr）.N‐acetyl‐beta‐D‐glucosaminidase,lactate dehydrogenase,alkaline phosphatase in urine were depressed to （125.49±11.68） U/（g Cr）,（103.73±21.79） U/（g Cr）,（101.99±12.28） U/（g Cr）,and （113.19±23.74） U/（g Cr）,（71.14±21.80） U/（g Cr）,（73.64±21.51） U/（g Cr） in procyanidins and lycopene groups.Indicators of oxidative stress,for example,Glutathion was reduced to （45.58±9.89） μmol/（g pro） and （45.33±5.90） μmol/（g pro）,and antioxidant enzymes such as superoxide dismutase,glutathione‐peroxidase were enhanced to （43.07±10.97） U/（mg pro） and （39.94±6.04） U/（mg pro）,（83.85±18.48） U/（mg pro）,and （85.62±12.68） U/（mg pro）.Malondialdehyde was lowered to （0.95±0.12） （μmol/g pro） and （1.03±0.12） μmol/（g pro） in procyanidins and lycopene groups.ROS generation was decreased by 27.63% and 16.40% and apoptosis was also decreased in procyanidins and lycopene groups respectively.Pathological changes were much better as well.Conclusion Procyanidins and Lycopene play some protective role against mercury kidney damage.展开更多
BACKGROUND This case report addresses the dearth of effective therapeutic interventions for central nervous system metastases in patients with HER2-negative breast cancer.It presents a unique case of a woman with estr...BACKGROUND This case report addresses the dearth of effective therapeutic interventions for central nervous system metastases in patients with HER2-negative breast cancer.It presents a unique case of a woman with estrogen receptor-positive,HER2-negative breast cancer who developed brain metastasis.The report highlights her initial favorable response to abemaciclib and letrozole therapy prior to the discon-tinuation due to drug-induced lung damage(DILD).CASE SUMMARY In this comprehensive case summary,we present the clinical course of a woman in her 60s,who 11 years following primary breast cancer surgery,was diagnosed with multiple brain metastases.As a third-line systemic therapy,she underwent treatment with abemaciclib and letrozole.This treatment approach yielded a near-partial response in her metastatic brain lesions.However,abemaciclib adminis-tration ceased due to the emergence of DILD,as confirmed by a computed tomography scan.The DILD improved after 1 mo of cessation.Despite ongoing therapeutic efforts,the patient’s condition progressively deteriorated,ultimately resulting in death due to progression of the brain metastases.CONCLUSION This case underscores the challenge of managing adverse events in responsive brain metastasis patients,given the scarcity of therapeutic options.展开更多
Objective:To investigate the protective effects and mechanism of antioxidant TBHQ on renal damage caused by doxorubicin chemotherapy in mice with hepatic cancer.Methods:Cell H22 of mice with hepatic cancer which was s...Objective:To investigate the protective effects and mechanism of antioxidant TBHQ on renal damage caused by doxorubicin chemotherapy in mice with hepatic cancer.Methods:Cell H22 of mice with hepatic cancer which was subcultured for three times was subcutaneously transplanted to the groin of right lower limb of 45 SPF Kunming mice to establish the transplanted tumor model.The doxorubicin chemotherapy group and antioxidant intervention group received intraperitoneal injection of ADM(1 mg/kg·0.2 mL/2d).The model control group received normal saline(NS) of the same volume at the same time.1%TBHQ was added into the diet of mice of the antioxidant intervention group.Seven weeks later,morning urines and peripheral blood were randomly collected to detect UAIb,UCr,BUN,Scr and UAlb/Cr levels.All mice were beheaded.The renal tissues were made into homogenate,and SOD,T-AOC and MDA content in tissues were detected followed by cell lysis.All data were processed using SPSS 19.0.Results:The UAlb/Cr,BUN.Scr and MDA of doxorubicin chemotherapy group were significantly higher those of model control group and the activities of SOD,T-AOC in doxorubicin chemotherapy group were lower than those of model control group(P<0.01).The UAlb/Cr,BUN,Scr and MDA of antioxidant intervention group were lower than those of doxorubicin chemotherapy group and the activities of SOD,T-AOC of antioxidant intervention group were higher than those of doxorubicin chemotherapy group doxorubicin chemotherapy group(P<0.05).The BUN of model control group was higher than that of blank group,and T-AOC was lower than that of blank group,and difference was statistically significant(P<0.05).Conclusions:Doxorubicin chemotherapy could lead to abnormal antioxidant capacity and renal function of tumor-bearing mice with hepatic cancer.TBHQ antioxidant intervention could effectively improve the antioxidant capacity of renal tissue and reduce the renal damage caused by doxorubicin to some extent.展开更多
In an attempt to understand the effects of high energy shock wave (HESW)on renal function, we studied prospectively 40 patients with nephrolithiasis in 4 groups,using same voltage with different numbers of shock wave ...In an attempt to understand the effects of high energy shock wave (HESW)on renal function, we studied prospectively 40 patients with nephrolithiasis in 4 groups,using same voltage with different numbers of shock wave therapy to identify the difference of effects on renal function. Stone burdens and posit ion were similar in these groups. Each group received 1500, 2000, 2500 or 3000 puises at 12. 5 KV on JT-3lithotripotor respectively. All the groups had significantly increased the levels of urinary NAG, β2MG, ALB and serum β2MG, which reached the highest values on 1-3days after ESWL (P<0. 001), and then decreased to the pre-ESWL levels except urinary NAG in group Cand D and serum β2MG which were still significantly higher (P<0.05) than those before-ESWL on the 7th day after ESWL. There was significant correlation between either urinary NAG (γ=0. 977, P<0. 05) or β2MG (γ=0. 933, P<0. 001) with the number of shock wave. In addition, urinary NAG and β2MG increased significantly when the number of shock waves was over 2500 shots.These above findings suggest that shock wave had induced acute changes in renal functions and transient renal tubular damages, although these functional changes recovered within one week, and the tubular damage might last longer than 7 days , In order to avoid serious renal damage, it’s necessary to limit the energy level of shock waves under 12. 5 KV×2500 shots by using JT-3 lithotriptor.展开更多
Diabetes mellitus(DM) is a chronic metabolic disorder characterized by a combination of hyperglycemia, reduced insulin sensitivity, and/or relative impairment of insulin secretion[1]. Renal damage, which is a major mi...Diabetes mellitus(DM) is a chronic metabolic disorder characterized by a combination of hyperglycemia, reduced insulin sensitivity, and/or relative impairment of insulin secretion[1]. Renal damage, which is a major microvascular complication of DM and a progressive kidney disease, has been considered the most common cause of end-stage renal disease[2]. Renal fibrosis is a common outcome of progressive renal damage.展开更多
Objective:To study the correlation of renal arterial ultrasound parameters with renal damage and placental hypoxia in patients with preeclampsia.Methods: A total of 56 cases of pregnant women who were diagnosed with p...Objective:To study the correlation of renal arterial ultrasound parameters with renal damage and placental hypoxia in patients with preeclampsia.Methods: A total of 56 cases of pregnant women who were diagnosed with preeclampsia in Mianyang People's Hospital between May 2014 and October 2016 were selected as the PE group of the research, and healthy pregnant women who received antenatal care during the same period were selected as the control group. Color Doppler diasonograph was used to determine renal arterial blood flow parameters, and enzyme-linked immunosorbent assay kits were used to determine the contents of renal damage and endothelial injury indexes in serum as well as the contents of apoptosis molecules caused by hypoxia in placenta.Results: Renal interlobar arterial Vs, Vd and AT levels in PE group were significantly higher than those in control group;CysC,β2-MG, sFlt-1, sEng, ET-1, AnnexinV and vWF contents in serum as well as KIM-1 and NGAL contents in urine of PE group were significantly higher than those of control group and positively correlated with renal interlobar arterial Vs, Vd and AT levels, and the ROS, CytC, Caspase-3 and Caspase-9 contents in placenta were significantly higher than those of control group and positively correlated with renal interlobar arterial Vs, Vd and AT levels.Conclusion: The change of renal arterial blood flow parameters in patients with preeclampsia can assess the extent of renal damage and placental hypoxia.展开更多
Objective:To study the renal function, peroxidation damage and inflammatory injury after epalrestat combined with alprostadil treatment of early diabetic nephropathy.Methods:90 patients with early diabetic nephropathy...Objective:To study the renal function, peroxidation damage and inflammatory injury after epalrestat combined with alprostadil treatment of early diabetic nephropathy.Methods:90 patients with early diabetic nephropathy treated in our hospital between June 2011 and November 2015 were collected and divided into observation group and control group (n=45) according to the single-blind randomized control method. Observation group received epalrestat combined with alprostadil treatment, control group received alprostadil treatment alone, and the treatment of both groups lasted for 3 months. Before treatment and after 3 months of treatment, turbidimetric immunoassay was used to detect the renal function indexes in peripheral blood, rate method was used to detect the renal function indexes in urine, and ELISA method was used to detect the levels of peroxidation indexes and inflammation indexes.Results:Before treatment, differences in renal function, peroxidation damage and inflammatory damage indexes were not statistically significant between two groups of patients (P>0.05). After 3 months of treatment, creatinine (Scr), cystatin C (CysC),β2 microglobulin (β2-MG), N-acetyl-β-D-glucosaminidase (NAG), reactive oxygen species (ROS), advanced protein oxidation products (AOPPs), interleukin-8 (IL-8), interleukin-27 (IL-27) and procalcitonin (PCT) levels of observation group were lower than those of control group while catalase (CAT), total superoxide dismutase (TSOD), interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-13 (IL-13) levels were higher than those of control group (P<0.05). Conclusions:Epalrestat combined with alprostadil can protect the renal function and inhibit the peroxidation damage and inflammatory injury in patients with early diabetic nephropathy.展开更多
This work aimed to find the effect of cranberry extract (75 and 150 mg/kg·b·w) and vit. C (1 g/kg·b·w orally) on renal toxicity induced by Diclofenac sodium in male albino r...This work aimed to find the effect of cranberry extract (75 and 150 mg/kg·b·w) and vit. C (1 g/kg·b·w orally) on renal toxicity induced by Diclofenac sodium in male albino rats. Treated rats with diclofenac sodium with a concentration 150 mg/kg·b·w, expressed a significant increase in several parameters includes, plasma total cholesterol, LDL-cholesterol, and triglyceride as well as renal nitric oxide (NO), tumor necrosis factor-alfa (TNF-α) and TBARS. In addition, a significant reduction in renal superoxide dismutase (SOD), GSH, catalase (CAT) and plasma HDL. The present results explain that, using cranberry extract and vit. C resulted in increasing the level of GSH, CAT and SOD as well as gene expression of renal SOD, CAT and IL-22 and reduce the level of TBARs significantly which led to preventing renal tissue damage. Our results also revealed that cranberry extract can protect DNA from damage as obtained from comet essay. TM-U was elevated in DCLF treated group when compared with normal. However cranberry extract was able to reduce this elevation in dose dependant manner. Histological features in H&E taken to different groups also mirrors this findings. DCLF causes many changes in renal tissue include infiltration by inflammatory cells, attenuated glomeruli, apoptosis in tubular epithelia.展开更多
BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differenti...BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.展开更多
文摘Objective This study aims to investigate the protection of procyanidins and lycopene from the renal damage induced by mercuric chloride.Methods Rats were treated with either procyanidins or lycopene 2h before HgCl 2 subcutaneously injection,once daily treatment for 2 successive days.Results In comparison with HgCl 2 group,markers of renal function such as blood urea nitrogen in serum and urinary protein were decreased to （18.45±11.63） mmol/L and （15.93±9.36） mmol/L,（4.54±0.78） g/（g Cr） and （4.40±1.12） g/（g Cr）.N‐acetyl‐beta‐D‐glucosaminidase,lactate dehydrogenase,alkaline phosphatase in urine were depressed to （125.49±11.68） U/（g Cr）,（103.73±21.79） U/（g Cr）,（101.99±12.28） U/（g Cr）,and （113.19±23.74） U/（g Cr）,（71.14±21.80） U/（g Cr）,（73.64±21.51） U/（g Cr） in procyanidins and lycopene groups.Indicators of oxidative stress,for example,Glutathion was reduced to （45.58±9.89） μmol/（g pro） and （45.33±5.90） μmol/（g pro）,and antioxidant enzymes such as superoxide dismutase,glutathione‐peroxidase were enhanced to （43.07±10.97） U/（mg pro） and （39.94±6.04） U/（mg pro）,（83.85±18.48） U/（mg pro）,and （85.62±12.68） U/（mg pro）.Malondialdehyde was lowered to （0.95±0.12） （μmol/g pro） and （1.03±0.12） μmol/（g pro） in procyanidins and lycopene groups.ROS generation was decreased by 27.63% and 16.40% and apoptosis was also decreased in procyanidins and lycopene groups respectively.Pathological changes were much better as well.Conclusion Procyanidins and Lycopene play some protective role against mercury kidney damage.
文摘BACKGROUND This case report addresses the dearth of effective therapeutic interventions for central nervous system metastases in patients with HER2-negative breast cancer.It presents a unique case of a woman with estrogen receptor-positive,HER2-negative breast cancer who developed brain metastasis.The report highlights her initial favorable response to abemaciclib and letrozole therapy prior to the discon-tinuation due to drug-induced lung damage(DILD).CASE SUMMARY In this comprehensive case summary,we present the clinical course of a woman in her 60s,who 11 years following primary breast cancer surgery,was diagnosed with multiple brain metastases.As a third-line systemic therapy,she underwent treatment with abemaciclib and letrozole.This treatment approach yielded a near-partial response in her metastatic brain lesions.However,abemaciclib adminis-tration ceased due to the emergence of DILD,as confirmed by a computed tomography scan.The DILD improved after 1 mo of cessation.Despite ongoing therapeutic efforts,the patient’s condition progressively deteriorated,ultimately resulting in death due to progression of the brain metastases.CONCLUSION This case underscores the challenge of managing adverse events in responsive brain metastasis patients,given the scarcity of therapeutic options.
文摘Objective:To investigate the protective effects and mechanism of antioxidant TBHQ on renal damage caused by doxorubicin chemotherapy in mice with hepatic cancer.Methods:Cell H22 of mice with hepatic cancer which was subcultured for three times was subcutaneously transplanted to the groin of right lower limb of 45 SPF Kunming mice to establish the transplanted tumor model.The doxorubicin chemotherapy group and antioxidant intervention group received intraperitoneal injection of ADM(1 mg/kg·0.2 mL/2d).The model control group received normal saline(NS) of the same volume at the same time.1%TBHQ was added into the diet of mice of the antioxidant intervention group.Seven weeks later,morning urines and peripheral blood were randomly collected to detect UAIb,UCr,BUN,Scr and UAlb/Cr levels.All mice were beheaded.The renal tissues were made into homogenate,and SOD,T-AOC and MDA content in tissues were detected followed by cell lysis.All data were processed using SPSS 19.0.Results:The UAlb/Cr,BUN.Scr and MDA of doxorubicin chemotherapy group were significantly higher those of model control group and the activities of SOD,T-AOC in doxorubicin chemotherapy group were lower than those of model control group(P<0.01).The UAlb/Cr,BUN,Scr and MDA of antioxidant intervention group were lower than those of doxorubicin chemotherapy group and the activities of SOD,T-AOC of antioxidant intervention group were higher than those of doxorubicin chemotherapy group doxorubicin chemotherapy group(P<0.05).The BUN of model control group was higher than that of blank group,and T-AOC was lower than that of blank group,and difference was statistically significant(P<0.05).Conclusions:Doxorubicin chemotherapy could lead to abnormal antioxidant capacity and renal function of tumor-bearing mice with hepatic cancer.TBHQ antioxidant intervention could effectively improve the antioxidant capacity of renal tissue and reduce the renal damage caused by doxorubicin to some extent.
文摘In an attempt to understand the effects of high energy shock wave (HESW)on renal function, we studied prospectively 40 patients with nephrolithiasis in 4 groups,using same voltage with different numbers of shock wave therapy to identify the difference of effects on renal function. Stone burdens and posit ion were similar in these groups. Each group received 1500, 2000, 2500 or 3000 puises at 12. 5 KV on JT-3lithotripotor respectively. All the groups had significantly increased the levels of urinary NAG, β2MG, ALB and serum β2MG, which reached the highest values on 1-3days after ESWL (P<0. 001), and then decreased to the pre-ESWL levels except urinary NAG in group Cand D and serum β2MG which were still significantly higher (P<0.05) than those before-ESWL on the 7th day after ESWL. There was significant correlation between either urinary NAG (γ=0. 977, P<0. 05) or β2MG (γ=0. 933, P<0. 001) with the number of shock wave. In addition, urinary NAG and β2MG increased significantly when the number of shock waves was over 2500 shots.These above findings suggest that shock wave had induced acute changes in renal functions and transient renal tubular damages, although these functional changes recovered within one week, and the tubular damage might last longer than 7 days , In order to avoid serious renal damage, it’s necessary to limit the energy level of shock waves under 12. 5 KV×2500 shots by using JT-3 lithotriptor.
基金supported by the National Nature Science Foundation of China [81572626 and 82003454]Chinese Nutrition Society-Bright Moon Seaweed Group Nutrition and Health Research Fund [CNS-BMSG2020A63]+1 种基金Chinese Nutrition Society-Zhendong National Physical Fitness and Health Research Fund [CNS-ZD2019066]Key R&D and Promotion Projects in Henan Province [212102310219]。
文摘Diabetes mellitus(DM) is a chronic metabolic disorder characterized by a combination of hyperglycemia, reduced insulin sensitivity, and/or relative impairment of insulin secretion[1]. Renal damage, which is a major microvascular complication of DM and a progressive kidney disease, has been considered the most common cause of end-stage renal disease[2]. Renal fibrosis is a common outcome of progressive renal damage.
文摘Objective:To study the correlation of renal arterial ultrasound parameters with renal damage and placental hypoxia in patients with preeclampsia.Methods: A total of 56 cases of pregnant women who were diagnosed with preeclampsia in Mianyang People's Hospital between May 2014 and October 2016 were selected as the PE group of the research, and healthy pregnant women who received antenatal care during the same period were selected as the control group. Color Doppler diasonograph was used to determine renal arterial blood flow parameters, and enzyme-linked immunosorbent assay kits were used to determine the contents of renal damage and endothelial injury indexes in serum as well as the contents of apoptosis molecules caused by hypoxia in placenta.Results: Renal interlobar arterial Vs, Vd and AT levels in PE group were significantly higher than those in control group;CysC,β2-MG, sFlt-1, sEng, ET-1, AnnexinV and vWF contents in serum as well as KIM-1 and NGAL contents in urine of PE group were significantly higher than those of control group and positively correlated with renal interlobar arterial Vs, Vd and AT levels, and the ROS, CytC, Caspase-3 and Caspase-9 contents in placenta were significantly higher than those of control group and positively correlated with renal interlobar arterial Vs, Vd and AT levels.Conclusion: The change of renal arterial blood flow parameters in patients with preeclampsia can assess the extent of renal damage and placental hypoxia.
文摘Objective:To study the renal function, peroxidation damage and inflammatory injury after epalrestat combined with alprostadil treatment of early diabetic nephropathy.Methods:90 patients with early diabetic nephropathy treated in our hospital between June 2011 and November 2015 were collected and divided into observation group and control group (n=45) according to the single-blind randomized control method. Observation group received epalrestat combined with alprostadil treatment, control group received alprostadil treatment alone, and the treatment of both groups lasted for 3 months. Before treatment and after 3 months of treatment, turbidimetric immunoassay was used to detect the renal function indexes in peripheral blood, rate method was used to detect the renal function indexes in urine, and ELISA method was used to detect the levels of peroxidation indexes and inflammation indexes.Results:Before treatment, differences in renal function, peroxidation damage and inflammatory damage indexes were not statistically significant between two groups of patients (P>0.05). After 3 months of treatment, creatinine (Scr), cystatin C (CysC),β2 microglobulin (β2-MG), N-acetyl-β-D-glucosaminidase (NAG), reactive oxygen species (ROS), advanced protein oxidation products (AOPPs), interleukin-8 (IL-8), interleukin-27 (IL-27) and procalcitonin (PCT) levels of observation group were lower than those of control group while catalase (CAT), total superoxide dismutase (TSOD), interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-13 (IL-13) levels were higher than those of control group (P<0.05). Conclusions:Epalrestat combined with alprostadil can protect the renal function and inhibit the peroxidation damage and inflammatory injury in patients with early diabetic nephropathy.
文摘This work aimed to find the effect of cranberry extract (75 and 150 mg/kg·b·w) and vit. C (1 g/kg·b·w orally) on renal toxicity induced by Diclofenac sodium in male albino rats. Treated rats with diclofenac sodium with a concentration 150 mg/kg·b·w, expressed a significant increase in several parameters includes, plasma total cholesterol, LDL-cholesterol, and triglyceride as well as renal nitric oxide (NO), tumor necrosis factor-alfa (TNF-α) and TBARS. In addition, a significant reduction in renal superoxide dismutase (SOD), GSH, catalase (CAT) and plasma HDL. The present results explain that, using cranberry extract and vit. C resulted in increasing the level of GSH, CAT and SOD as well as gene expression of renal SOD, CAT and IL-22 and reduce the level of TBARs significantly which led to preventing renal tissue damage. Our results also revealed that cranberry extract can protect DNA from damage as obtained from comet essay. TM-U was elevated in DCLF treated group when compared with normal. However cranberry extract was able to reduce this elevation in dose dependant manner. Histological features in H&E taken to different groups also mirrors this findings. DCLF causes many changes in renal tissue include infiltration by inflammatory cells, attenuated glomeruli, apoptosis in tubular epithelia.
基金Supported by the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China,No.LHDMZ22H050001the Construction of Key Projects by Zhejiang Provincial Ministry,No.WKJ-ZJ-2302+3 种基金the Zhejiang Province Chinese Medicine Modernization Program,No.2020ZX001the Key Project of Scientific Research Foundation of Chinese Medicine,No.2022ZZ002the“Pioneer”and“LeadingGoose”R&D Program of Zhejiang,No.2022C03118 and 2023C03075the Key Project of Basic Scientific Research Operating Funds of Hangzhou Medical College,No.KYZD202002.
文摘BACKGROUND Diabetic kidney disease(DKD)is a major complication of diabetes mellitus.Renal tubular epithelial cell(TEC)damage,which is strongly associated with the inflammatory response and mesenchymal trans-differentiation,plays a significant role in DKD;However,the precise molecular mechanism is unknown.The recently identified microRNA-630(miR-630)has been hypothesized to be closely associated with cell migration,apoptosis,and autophagy.However,the association between miR-630 and DKD and the underlying mechanism remain unknown.AIM To investigate how miR-630 affects TEC injury and the inflammatory response in DKD rats.METHODS Streptozotocin was administered to six-week-old male rats to create a hypergly cemic diabetic model.In the second week of modeling,the rats were divided into control,DKD,negative control of lentivirus,and miR-630 overexpression groups.After 8 wk,urine and blood samples were collected for the kidney injury assays,and renal tissues were removed for further molecular assays.The target gene for miR-630 was predicted using bioinformatics,and the association between miR-630 and toll-like receptor 4(TLR4)was confirmed using in vitro investigations and double luciferase reporter gene assays.Overexpression of miR-630 in DKD rats led to changes in body weight,renal weight index,basic blood parameters and histopathological changes.RESULTS The expression level of miR-630 was reduced in the kidney tissue of rats with DKD(P<0.05).The miR-630 and TLR4 expressions in rat renal TECs(NRK-52E)were measured using quantitative reverse transcription polymerase chain reaction.The mRNA expression level of miR-630 was significantly lower in the high-glucose(HG)and HG+mimic negative control(NC)groups than in the normal glucose(NG)group(P<0.05).In contrast,the mRNA expression level of TLR4 was significantly higher in these groups(P<0.05).However,miR-630 mRNA expression increased and TLR4 mRNA expression significantly decreased in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Furthermore,the levels of tumor necrosis factor-alpha(TNF-α),interleukin-1β(IL-1β),and IL-6 were significantly higher in the HG and HG+mimic NC groups than in NG group(P<0.05).However,the levels of these cytokines were significantly lower in the HG+miR-630 mimic group than in the HG+mimic NC group(P<0.05).Notably,changes in protein expression were observed.The HG and HG+mimic NC groups showed a significant decrease in E-cadherin protein expression,whereas TLR4,α-smooth muscle actin(SMA),and collagen IV protein expression increased(P<0.05).Conversely,the HG+miR-630 mimic group exhibited a significant increase in E-cadherin protein expression and a notable decrease in TLR4,α-SMA,and collagen IV protein expression than in the HG+mimic NC group(P<0.05).The miR-630 targets TLR4 gene expression.In vivo experiments demonstrated that DKD rats treated with miR-630 agomir exhibited significantly higher miR-630 mRNA expression than DKD rats injected with agomir NC.Additionally,rats treated with miR-630 agomir showed significant reductions in urinary albumin,blood glucose,TLR4,and proinflammatory markers(TNF-α,IL-1β,and IL-6)expression levels(P<0.05).Moreover,these rats exhibited fewer kidney lesions and reduced infiltration of inflammatory cells.CONCLUSION MiR-630 may inhibit the inflammatory reaction of DKD by targeting TLR4,and has a protective effect on DKD.
