艾塞那肽对糖尿病肾病小鼠足细胞的保护作用

目的:探讨艾塞那肽对糖尿病肾病小鼠足细胞的作用。方法:通过给予C57BL/6J小鼠高脂饮食并注射链脲佐菌素建立糖尿病肾病模型，按随机数字表法将其分为糖尿病肾病对照组(DN组， n＝8)、艾塞那肽干预组(DN＋Ex组， n＝8)。同时将普通饲料喂养的C57BL/6J小鼠作为正常对照组(NC组， ...

Protective effect of exenatide on podocyte in diabetic nephropathy mice

Objective To investigate the effects of exenatide on podocyte in diabetic nephropathy mice.Methods Diabetic nephropathy mice models were induced by using streptozocin-treated C57BL/6J mice on high fat diets,which were randomized by random number table to diabetic nephropathy control group(DN group,n=8)and exenatide treatment diabetic nephropathy group(DN+Ex group,n=8).The C57BL/6J mice on normal chow diet were used as normal control group(NC group,n=8).After the intervention,blood glucose,renal function,and urine albumin/creatinine ratio were measured.Pathological glomerular changes were observed by pexiodic acid-Schiff stain(PAS)staining.The mRNA expression of profibrotic molecules CollagenⅣ,transforming growth factor-β(TGF-β),and Fibronectin in glomerular lysates were measured by realtime quantitative PCR(RT-PCR).Podocyte injury and apoptosis were evaluated by immunofluorescent staining and transmission electron microscopy.The expression of Nephrin,Cleaved caspase-3,protein kinase B(Akt),and phosphorylated Akt(p-Akt)in glomerular lysates were examined by western blotting.Results Compared with the DN group,urine albumin/creatinine ratio was significantly decreased in the DN+Ex group(P<0.01).PAS staining and analysis found that exenatide administration ameliorated mesangial matrix expansion and glomerular hypertrophyin in DN group(P<0.05).RT-PCR analyses showed that the glomerular expression for Fibronectin,TGF-β,and CollagenⅣwere significantly decreased in the DN+Ex group compared with the DN group(P<0.01).Immunofluorescent staining and transmission electron microscopy revealed that exenatide treatment improved podocyte injury and apoptosis in DN group.Western blotting analyses showed that exenatide increased the Nephrin expression,decreased the Cleaved caspase-3 expression,increased the p-Akt expression in glomerular lysatesin diabetic nephropathy mice(P<0.01).Conclusion Exenatide attenuates podocyte injury and apoptosis and proteinuria,and prevents the progression of diabetic nephropathy mice.Phosphatidylinositol 3-kinase(PI3K)/Akt pathway in glomerular lysates may be related to the protective effects of exenatide.