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目的:探讨尿液中足细胞检测在糖尿病肾病(DN)大鼠中的意义,贝那普利、氯沙坦对DN大鼠足细胞的表达及排泄的影响。方法:32只DN大鼠随机分为4组:A组:糖尿病肾病模型组;B组:贝那普利组;C组:氯沙坦组;D组:贝那普利+氯沙坦组。腹腔注射链佐脲菌素诱导DN大鼠模型。实验12周时检测24h尿蛋白定量(TP),总胆固醇(TC)。间接免疫荧光法检测尿沉渣足细胞特异性标志蛋白podocalyxin以检测尿液足细胞(UPC)水平;免疫荧光染色观察肾小球上皮细胞蛋白-1( GLEPP1)的表达。结果:A组UPC、TP较B、C组明显升高(P<0.01),TC亦较B、C组升高(P<0.05)。B、C组UPC、TP、TC无显著性差异(P>0.05)。与B、C组相比,D组显著降低TP(P<0.01),UPC及TC(P<0.05)。病理组织肾小球荧光染色示GLEEPP1在A组呈节段性明显缺失,B、C组缺失较轻,D组无明显缺失。UPC与TP正相关(r_s=0.54,P<0.05),而与TC无显著相关性(r_s=0.35,P>0.05)。结论:尿液中脱落足细胞检测可作为判断DN病情活动性的标志之一。贝那普利、氯沙坦均可减少DN大鼠蛋白尿,降低胆固醇,减少足细胞脱落及尿液足细胞的排泄,且两者效果相似,而两者联用较单用一种可显著减少足细胞排泄,降低蛋白尿及胆固醇,肾保护作用更为明显。
Objective: To investigate the significance of urinary podocyte detection in diabetic nephropathy (DN) rats and the effects of benazepril and losartan on the expression and excretion of podocytes in DN rats. Methods: Thirty-two DN rats were randomly divided into 4 groups: group A: diabetic nephropathy model group; group B: benazepril group; group C: losartan group; group D: benazepril + losartan group . Intraperitoneal injection of streptavidin induced DN rat model. Urine protein (TP) and total cholesterol (TC) were measured 24 hours after the experiment. Indirect immunofluorescence was used to detect podocalyxin, a specific marker of urinary sediment, to detect the level of urinary podocytes (UPC). The expression of glomerular epithelial cell protein-1 (GLEPP1) was detected by immunofluorescence staining. Results: UPC and TP of group A were significantly higher than those of group B and C (P <0.01), and TC of group A was also higher than that of group B and C (P <0.05). There was no significant difference in UPC, TP and TC between B and C groups (P> 0.05). Compared with B and C groups, D group significantly reduced TP (P <0.01), UPC and TC (P <0.05). Glomerular fluorescence staining showed that GLEEPP1 was significantly deleted in group A, segmental loss in group B and C, and no obvious loss in group D. UPC was positively correlated with TP (r_s = 0.54, P <0.05), but not with TC (r_s = 0.35, P> 0.05). Conclusion: The detection of shedding podocytes in urine can be used as one of the markers to judge the activity of DN. Both benazepril and losartan decreased proteinuria, decreased cholesterol, reduced shedding of podocytes and excretion of urinary podocytes, both of which were similar Reduce podocyte excretion, reduce proteinuria and cholesterol, the protective effect of kidney is more obvious.