贝那普利、氯沙坦对糖尿病肾病大鼠足细胞表达及排泄的影响

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。

Influence of Benazepril and Losartan on the Expression of Podocytes and Urinary Podocytes Excretion in Rats with Diabetic Nephropathy

Objective:To investigate the clinical significance of detecting the urinary podocytes (UPC) excretion and the influence of benazepril and losartan on the expression of podocytes and urinary pedocytes excretion in rats with diabetic nephropathy(DN).Meth- od:The experiments were performed on 32 DN rats.The rats were randomly divided into four groups:diabetic nephropathy model group (group A),treated with benazepril group(group B),treated with losartan group(group C),treated with benazepril and losartan group (group D).DN rats were induced with streptozotocin (STZ) in peritoneal injection.24h total proteinuria (TP),Total cholesterol (TC) and UPC were measured at 12 weeks.Podoeyte-specific marker protein-podocalyxin(PCX) was detected by immunofluoreseene.The expression of glomerular epithelial cell membrane protein-tyrosine phosphatase 1 (GLEPP1) was observed by immunofluorescene.Re- sult:UPC,TP in group A were significantly higher than those in group B and C(P<0.01),TC was also increased than those in group B and C (P<0.05).UPC,TP and TC had no statistic difference between group B and C (P>0.05).Group D decreased the level of TP (P<0.01),UPC and TC(P<0.05) than that in group B and C respectively.Histologically,focal absence of the expression of GLEPP1 was seen in group A in glomeruli by immunofluorescene,focal absence was slight in group B and C,was not obviously ab- sence in group D.The levels of UPC showed a positive correlation with TP(r_s=0.54,P<0.05),had no correlation with TC(r_s= 0.35,P>0.05).Conclusion:Urinary podocyte can be one of the markers to predict the development of DN.Benazepril and losartan can contribute to decrease proteinuria,TC and urinary excretion of podocytes.Combined with benazepril and losartan treatment decreas the level of podocytes excrection,proteinuria,TC than that by single benazepril and losartan.The effect of combined benazepril and losartan to protect kidney is more pronounced than by single therapy.