·糖尿病基础研究·

　　盐酸吡格列酮对糖尿病大鼠肾组织nephrin表达的影响

　　匡蕾 叶山东 邢燕 胡闻 陈玉米

　　【摘要】 目的 观察不同剂量盐酸吡格列酮(PIO)对糖尿病大鼠肾脏保护作用。方法 将SD大鼠随机分为5组(n=8)：糖尿病模型(DM)组,10、20和30 mg/(kg·d)PIO干预组(DR1、DR2、DR3组)及正常对照(NC)组。8周末测BG，HbA1c，尿白蛋白(UAlb)，尿视黄醇结合蛋白(RBP)，尿沉渣nephrin(UNE)。留取肾组织观察病理变化及nephrin表达。结果 8周末UAlb、UNE、RBP、肾脏肥大指数(KI)、基底膜厚度(GBMT)、足突融合率(FPFR)DR1～3组均低于DM组，且DR2、3组低于DR1组(P<0.05);肾脏nephrin mRNA水平DM组>DR1～3组>NC组;肾脏nephrin蛋白：NC组>DR1～3组>DM组;nephrin mRNA及蛋白在DR1～3组间差异无统计学意义。UNE与UAlb、KI呈正相关。结论 PIO可通过调节足细胞nephrin蛋白及mRNA表达、抑制UNE，起到保护肾脏的作用，有一定的剂量依赖性。

　　【关键词】 糖尿病性肾脏疾病;nephrin;吡格列酮

Effect of pioglitazone on the expression of nephrin in the renal tissues of diabetic rats KUANG Lei, YE Shan-dong, XING Yan, et al. Department of Endocrinology, The Affiliated Provincial Hospital of Anhui Medical University, Hefei 230001, China

Corresponding author: YE Shan-dong, E-mail: ysd196406@163.com

　　【Abstract】Objective To investigate the protective effect of different dosages of pioglitazone (PIO) on the kidney of diabetic rats. Methods SD-rats were randomized into five groups: NC group, DM group, DR1, DR2 and DR3 groups, with 8 rats in each. The levels of blood glucose (BG), HbA1c, urinary albumin (UAlb), urinary retinol-binding protein (RBP), and urine sediment nephrin (UNE) were measured at the end of the 8th week, and the kidneys were microdissected for morphometric analysis and the observation of expression of podocyte nephrin. Results At the end of the 8th week, the levels of UAlb, UNE, RBP, kidney enlargement index (KI), glomerular basement membrane thickness (GBMT), and foot podocyte fusion rate (FPFR) decreased significantly in PIO-treatment groups in comparing with those of the DM group, in addition, these indices in the DR2 and DR3 group were lower than those in the DR1 group (P<0.05). The level of expression of podocyte nephrin mRNA in the DM group was >DR1～3 groups >NC group; the level of expression of kidney nephrin in the NC group was >DR1～3 groups >DM group; and there was no statistical difference in the level of expression of nephrin mRNA and protein among the DR1～3 groups. The level of UNE was positively correlated with those of Ualb and KI respectively (P<0.01). Conclusion The mechanism of PIO alleviating the kidney injury of diabetic rats is realized in part by in regulating the expressions of podocyte nephrin mRNA and protein and restraining UNE with a dose-dependent manner.

　　【Key words】 Diabetic nephropathy; Nephrin; Pioglitazone; Proteinuria