洛沙坦对糖尿病肾病大鼠足细胞nephrin及podocin表达的影响

Effects of Losartan to Podocyte Expression of Nephrin and Podocin in Diabetic Nephropathy Rats

目的探讨洛沙坦对糖尿病肾病大鼠足细胞超微结构及其相关分子nephrin、podocin表达的影响。方法将30只Wistar大鼠随机分为3组:正常对照组(N组)、糖尿病肾病组(D组)和洛沙坦干预组(L组)。L组大鼠给予洛沙坦50mg·kg-1·d-1灌胃,N组和D组大鼠给予等量饮用水灌胃。于第4周和第8周检测3组大鼠24h尿蛋白(Pro)量、血清肌酐(Scr)、三酰甘油(TG)和胆固醇(CHO)水平;用免疫组化、RT-PCR方法检测肾皮质nephrin、podocin蛋白及二者mRNA表达水平;用透射电镜检测足细胞超微结构变化。结果造模后第4周和第8周,D组大鼠24h Pro、Scr、TG、CHO水平与N组比较,差别有统计学意义(P<0.01);造模后第4周,L组大鼠24 hPro与D组比较,差别有统计学意义(P<0.05),造模后第8周,L组大鼠24h Pro和Scr水平与D组比较,差别有统计学意义(P<0.01)。第4周和第8周,D组大鼠nephrin及podocin蛋白表达水平与N组比较,差别有统计学意义(P<0.05);而且L组大鼠nephrin及podocin蛋白表达水平与D组比较,差别亦有统计学意义(P<0.05)。第4周和第8周,D组大鼠足细胞数、足突平均宽度(FPW)、足突融合率、基底膜厚度与N组比较,差别有统计学意义(P<0.01);L组大鼠足细胞数、FPW、足突融合率、基底膜厚度与D组比较,差别亦有统计学意义(P<0.01)。第4和第8周,D组大鼠nephrin mRNA和podocin mRNA表达水平与N组比较,差别有统计学意义(P<0.01);L组大鼠nephrin mRNA和podocin mRNA表达水平与D组大鼠比较,差别亦有统计学意义(P<0.05)。结论洛沙坦能通过上调nephrin和podocin表达水平来改善足细胞超微结构,减少糖尿病肾病大鼠蛋白尿。

Objective To investigate the effects of Iosanan on the uhrastructural changes of podocytes and the expression of relative molecules nephrin and podocin in diabetic nephropathy （DN） rats. Methods Totally 30 Wistar rats were divided into threes groups： normal control group （group N）, DN model group （group D）, treatment group with Iosartan （group L）. The rats in group L were by gavage given 50 mg · kg ^- 1 · d ^- 1, and for the rats in other two groups the same amount of fresh water was used. At the 4th and 8th weeks, quantification of 24 - hour proteinuria （24h Pro）, and the levels of serum creatinine （Scr）, triglyceride （TG） and cholesterol （CHO） were measured, The expressions of nephrin and podocin, and their mRNA in the renal cortex were detected by immunohistochemical technique and RT - PCR, and the ultrastructures of podocyte were measured by electron microscope, Results At the 4th and 8th weeks after the models were set up, compared to group N, the levels of 24h Pro, Scr, TG and CHO in group D showed significant differences （ P 〈0.01 ）. At the 4th week, the level of 24h in group L showed a significant difference （ P 〈0. 05）, and at 8th week, the levels of 24h Pro and Scr in group L showed significant differences （ P 〈0, 01 ）, as compared with those in the group D, At the 4th and 8th week, compared to group N, the levels of expressions of nephrin and podocin group D showed significant differences （ P 〈 0. 05 ）, and compared to group D, the levels of expressions of nephrin and podocin group L showed significant differences too （ P 〈0. 05 ）. At the 4th and 8th week, there were significant differences in the number of podocytes was lower, the average foot process width （FPW）, foot process fusion rate and basilar membrane thickness between the group D and group N （ P 〈0.01 ） ; and there were significant differences in the number of podocytes was lower, the average foot process width （ FPW）, foot process fusion rate and basilar membrane thickness between the group L and group D （ P 〈 0. 01 ）. At the 4th and 8th week, there were significant differences in the expressions of nephrin and podocin mRNA between the group D and group N （ P 〈0. 01 ） ; and there were significant differences in the expressions of nephrin and podocin mRNA between the group L and group D （ P 〈 0. 05）. Conclusion Losartan can improve the podocyte uhrastructure and reduce the proteinuria in DN rats through down - regulation of the expression of nephrin and podocin .