依那普利对糖尿病大鼠肾小管PKCα和BMP-7的调节

Regulation Effect of Enalapril on Protein Kinase Cα and Bone Morphogenetic Protein-7 in Renal Tubule of Diabetic Rat

目的:观察依那普利对糖尿病(DM)大鼠肾小管上皮细胞血管紧张素Ⅱ(ANGⅡ)、蛋白激酶Cα(PKCα)和骨形态发生蛋白-7(BMP-7)表达的影响,探讨依那普利对肾脏BMP-7的调节机制。方法:将SD大鼠分为正常对照组(CG)、糖尿病组(DG)和糖尿病依那普利治疗组(DET),以链脲佐菌素复制DM大鼠模型;12周后测定大鼠血糖、血肌酐和24 h尿蛋白及肾脏指数,免疫组织化学检测肾小管上皮细胞PKCα、ANGⅡ和FN蛋白的表达;RT-PCR方法检测肾皮质BMP-7和PKCα的水平。结果:与CG相比,DG大鼠血糖、血肌酐、24 h尿蛋白及肾脏指数均显著升高,肾小管上皮细胞PKCα蛋白及mRNA,ANGⅡ和FN蛋白表达明显增多,同时BMP-7mRNA表达明显减少;DET上述升高指标除血糖外均显著低于DG,而BMP-7mRNA的表达却明显增加。结论:依那普利可部分抑制ANGⅡ生成,并且可能通过减少PKCα的活化,促进内源性BMP-7的表达,改善糖尿病肾病。

Objective： To observe the effects of enalapril on the expression of angiotensinⅡ（ANGⅡ）,protein kinase Cα（PKCα） and bone morphogenetic protein-7（BMP-7） in renal tubules of diabetic rats,and to investigate it＇s regulatory mechanism to BMP-7.Methods： SD rats were divided into control group（group C）,diabetic group（group D） and diabetic enalapril-treated group（group E）.Diabetic model was established by injecting STZ through vena caudalis.Blood glucose（BG）,serum creatinine（Scr）,24 hours urine protein（UP） and kidney index were detected in 12 weeks.Expressions of PKCα,ANGⅡ,and FN protein in renal tubules of all groups were detected with immunohistochemistry methods.The mRNA levels of BMP-7 and PKCα in renal cortex were tested with RT-PCR.Results： The levels of BG,Scr,and UP,and kidney indexes were higher significantly in group D than those in group C.The expression of PKCα protein and mRNA,ANGⅡand FN protein in renal tubular cells were also increased obviously and BMP-7 mRNA decreased remarkably in group D than those in group C.In group E,the increased parameters mentioned above except BG were significantly lower than those in group D,but BMP-7 mRNA was up-regulated notably.Conclusions： Enalapril can partially inhibiting ANGⅡproduction,and to promote endogenous BMP-7 expression by reducing activation of PKCα,by which enalapril can relieve diabetic nephropathy.