氯沙坦对Nestin在糖尿病大鼠肾组织中表达的影响

目的研究中间丝蛋白Nestin在糖尿病大鼠肾组织中的表达以及血管紧张素Ⅱ受体1拮抗剂(AT1Ra)氯沙坦的影响。方法雄性Wistar大鼠30只,随机分出正常对照组(N组)10只,余20只腹腔注射STZ制备糖尿病大鼠模型。模型制备成功后,再随机分为糖尿病组(DM组)10只和氯沙坦治疗组(DL组)10只。DL组大鼠每日给予氯沙坦20 mg/kg灌胃。干预8 w后,生化方法检测各组大鼠血糖、血尿素氮(BUN)及24 h尿蛋白。电镜观察足细胞超微结构变化;免疫组织化学、流式细胞术、Wertern印迹检测肾组织中Nestin蛋白的表达。结果 DM组大鼠Nestin蛋白表达明显高于N组;氯沙坦治疗后,Nestin表达明显降低。相关性分析显示,Nestin蛋白表达水平与24 h尿蛋白量密切相关(P<0.01)。结论Nestin表达升高可能参与了糖尿病大鼠蛋白尿的发生,氯沙坦对肾脏的保护作用可能部分的是通过降低Nestin的表达而实现的。

Effect of Iosartan on the expression of nestin in kidney of diabetic rats

Objective To explore the expression of nestin in renal tissue of diabetic rats,and the effects of losartan on it.Methods Male Wistar rats were randomly divided into normal group with 10 rats,the others were induced into diabetes by intraperitoneal injection of streptozotocin(STZ).When diabetic model was established,the rats were randomly divided into diabetes mellitus(DM) and losartan(DL) groups(n=10).The rats of DL group were treated with losartan 20 mg·kg-1·d-1.Blood glucose,serum urea nitrogen and 24 hours urine protein were examined by biochemistry methods after 8 weeks.Ultrastructure of podocyte was observed by electron microscope.The expression of nestin protein was examined by immunohistochemistry,flow cytometry and Western blot.Results Compared with that of control group,the expression of nestin protein was significantly increased in diabetic rats,which was down-regulated by losartan.It was closely related between nestin and proteinuria(P<0.01).Conclusions The expression of intermediate filament protein nestin might be up-regulated in diabetic rat renal,and probably take part in the development of proteinuria.Losartan maybe play protective role in diabetic kidneys by down-regulating nestin.