血管紧张素Ⅱ与糖尿病大鼠足细胞损害的实验研究  

Experimental study on angiotensin Ⅱ and podocyte injury in diabetic rats

作　　者：覃乔静[1] 邓华聪[1] 曹文富[1] 兰丽珍[1] 刘东方[1] 

机构地区：[1]重庆医科大学临床学院内分泌科,重庆400016

出　　处：《重庆医科大学学报》2004年第4期448-451,502,共5页Journal of Chongqing Medical University

摘　　要：目的 :研究血管紧张素Ⅱ (AngⅡ )在糖尿病大鼠肾小球滤过屏障外层足细胞损害中的作用 ,以探讨糖尿病肾病的发生机制。方法 :实验大鼠分为 3组 :正常对照组 (C)、糖尿病组 (D)和氯沙坦治疗病鼠组 (DT) ,实验第 5周末检测肾皮质超氧化物歧化酶 (SOD)、过氧化氢酶 (CAT)、丙二醛 (MDA)和尿白蛋白排泄率 (UAER)的水平 ,利用透射电子显微镜观察肾脏足细胞超微结构 ,同时用免疫组化技术检测肾小球足细胞损伤标志蛋白 -desmin蛋白的表达。结果 :与正常对照组比较 ,糖尿病组大鼠肾皮质SOD和CAT活性显著降低 ,而MDA含量明显增加 ,肾小球内desmin蛋白表达上调 ,足细胞部分足突融合 ,尿白蛋白排泄率增高 ;AngⅡ 1型受体拮抗剂氯沙坦明显减轻糖尿病大鼠肾皮质SOD、CAT、MDA及肾小球内desmin蛋白表达的改变 ,减轻足细胞足突融合 ,降低尿白蛋白排泄率。结论 :糖尿病时AngⅡ参与增高肾组织氧化应激 ,损害肾小球滤过屏障外层足细胞的结构和功能 。Objective:To investigate the role of angiotensin Ⅱ(Ang Ⅱ) in the injury of podocytes,last barrier of glomemlar filtration,to research the pathogenesis of diabetic nephropathy.Methods:The experimental rats were divided into three groups:control rats(group C),diabetic rats(group D)and diabetic rats treated by losartan(group DT).Urinary albumin excretion rate (UAER) was assayed 5 weeks after treatment.In addition,the activity of superoxide dismutase(SOD),catalase (CAT) and concentration of matondialdehyde(MDA) in renal cortex were measured.The podocyte ultrastructure was observed by transmission electronic microscopy while immunohistochemistry was used to detect the expression of desmin,a marker of podocyte injury.Results:Compared with control rats,the activity of SOD and CAT was decreased significantly and the concentrations of MDA were increased markedly in diabetic renal cortex.The expression of glomerular desmin increased markedly accompanied with foot process effacement in podocytes in diabetic group.At the same time,UAER increased in diabetes.The changes of SOD,CAT,MDA,glomemlar desmin expression,UAER and foot process effacement were markedly ameliorated after diabetic rats were treated by angiotensin Ⅱ type one receptor antagonist losartan.Conclusion:Ang Ⅱ may participate in the structural and functional damage of podocytes,last barrier of glomerular filtration,by increasing renal oxidative stress to injure kidney and accelerate proteinuria in diabetes.

关 键 词：糖尿病肾病 血管紧张素Ⅱ 氧化应激 足细胞 

分 类 号：R587.1[医药卫生—内分泌]