贝那普利对早期糖尿病肾脏疾病足细胞损伤保护作用的实验研究

Protective effect of Benazepril on podocyte injury in early diabetic nephropathy

目的探讨贝那普利对早期糖尿病肾脏疾病(DKD)足细胞损伤保护作用。方法选取SPF级雄性Wistar大鼠40只,随机分为正常对照(NC)组、单肾切除(SNE)组、DKD组和贝那普利(Ben)组,每组10只,其中DKD组和Ben组采用60mg/kg STZ腹腔注射建立DKD模型,成模4周后,Ben组予10mg/(kg·d)贝那普利灌胃,DKD组、SNE组和NC组4周后予等量蒸馏水灌胃。检测各组生化指标,观察肾脏组织病理改变及足细胞超微结构,免疫荧光检测肾皮质Nephrin和Podocin蛋白表达。结果Ben组多饮多尿症状减轻,第4、8、12周体质量均高于DKD组(P<0.05);DKD组和Ben组血糖高于NC组、SNE组(P<0.05);DKD组Scr和24h尿蛋白定量高于NC组、SNE组,血清白蛋白低于NC组、单肾切除组(P<0.05);Ben组Scr和24h尿蛋白定量(81.30±20.46)μmol/L、(190.44±5.10)mg/24h低于DKD组,血清白蛋白(36.47±1.32)g/L高于DKD组(P<0.05);DKD组肾组织AT Ⅱ高于NC组(P<0.05);Ben组AT Ⅱ(14.60±0.82)pg/ml低于DKD组(P<0.05);DKD模型组足突宽度、足突融合率和基底膜厚度高于NC组、SNE组(P<0.05);Ben组足突宽度、足突融合率和基底膜厚度分别为(0.41±0.01)μm、(34.20%±6.81%)和(0.40±0.03)μm,低于DKD组(P<0.05);Ben组Nephrin和Podocin蛋白表达较DKD组升高。结论贝那普利对早期DKD足细胞有保护作用,其机制可能与降低肾组织ATⅡ,上调Nephrin和Podocin蛋白表达有关。

Objective To investigate the protective effect of Benazepril on podocyte injury in early diabetic kidney disease. Methods A total of 40 male SPF wistar rats were selected and randomly divided into normal control（NC） group, single nephrectomy（SNE） group, DKD group and Beuazepril（Ben） group, with 10 rats in each group. The DKD model was established by 60 mg/kg STZ intraperitoneal injection. Four weeks later,Ben group received intragastric administration of 10 mg/（kg, d） lotensin, while DKD, group,SNE group and NC group were treated with distilled water. Biochemical indexes were measured, and the pathological changes of kidney tissues and ultrastructure of podocytes were observed in each group. The expression of nephrin and podocin protein in renal cortex was detected by immunofluorescence method. Results Polyuria symptoms alleviated in Ben group. Body weight was higher in Ben group than in DKD group（P〈0.05） during 4 weeks, 8 weeks and 12 weeks follow up. Blood glucose was higher in DKD group and Ben group than in NC group and SNE group（P〈0.05）. Serum creatinine and 24 h urinary protein were significantly higher while albumin was significantly lower in DKD group than in NC group and SNE group（P〈0.05）. Serum ereatinine（81. 30!20. 46） μmol/L and 24 h urinary protein（190.44±5.10） mg/24 h were significantly lower, while albumin（36.47±1.32） g/L was significantly higher in Ben group than in DKD group（P〈0. 05）. Angiotensin II （AT Ⅱ） in renal tissue was higher in DKD group than in NC group（P〈0. 05）. Angiotensin Ⅱ（AT Ⅱ ） in renal tissue was lower in Ben group than in DKD group （P〈0. 05）. The foot process width, foot process fusion rate and thickness of the basement membrane were significantly lower in Ben group（0.41±0. 01） μm, （34. 20±6.81%） and （0. 40±0.03） μm, than in DKD group（P〈0. 05）. The expression of nephrin and podocin protein were higher in Ben group than in DKD group. Conclusion Benazepril has a protective effect in early diabetic nephropathy podocyte, which may be associated with the decrease of renal tissue AT Ⅱ, and increase of the expression of Nephrin and podocin protein.