依那普利对糖尿病大鼠肾小管BMP-7表达影响  

Effect of enalapril on expression of bone morphogenetic protein-7 (BMP-Ⅰ) in renal tubules of diabetic rat

作　　者：肖瑛[1] 石明隽[1] 桂华珍[1] 郭兵[1] 张国忠[1] 

机构地区：[1]贵阳医学院病理生理学教研室,贵州贵阳550004

出　　处：《中国公共卫生》2009年第9期1129-1131,共3页Chinese Journal of Public Health

基　　金：教育部博士学科专项基金(20060660001);贵州省优秀科技教育人才省长专项基金(2005-303)

摘　　要：目的探讨依那普利治疗糖尿病(DM)肾病作用机制。方法SD大鼠分为正常对照组、糖尿病组和依那普利治疗组。以链脲佐菌素复制DM模型。12周后测定血糖、血肌酐和24 h尿蛋白及肾脏指数;免疫组化检测肾小管上皮细胞骨形态发生蛋白-7(BMP-7)、蛋白激酶Cα(PKCα)、血管紧张素Ⅱ(ANGⅡ)和结缔组织生长因子(CTGF)表达;RT-PCR方法检测肾皮质相应指标基因的水平。结果与正常对照组比较,糖尿病组肾小管PKCα蛋白及mRNA,ANGⅡ、CTGF和FN蛋白表达分别增多了94.3%及62.2%,86.2%,93.6%和90.8%(P<0.05);而BMP-7蛋白及mRNA表达减少了21%及59.7%(P<0.05)。依那普利治疗组除血糖外较糖尿病组降低了31.6%及41.3%,40.2%,54.7%和24%(P<0.05);而BMP-7表达增加了21.1%,15.3%(P<0.05);依那普利治疗组BMP-7与PKCα、ANGⅡ、CTGF和FN表达呈负相关(r=-0.838,-0.885,-0.829和-0.931,P<0.05或P<0.01)。结论依那普利可部分抑制ANGⅡ生成,并通过PKCα和CTGF抑制BMP-7的表达从而改善糖尿病肾病。Objective To investigate the regulatory mechanism of enalapril to BMP-7 in diabetic nephropathy. Methotis SD rats were divided into control group and model group. The diabetes model was established by injecting STZ through vena caudalis, and the rats in the model group were divided randomly into diabetic group （DG） and diabetic enalapril-treated group（DEG）. After 12 weeks, blood glucose, creatinine and 24 hours urineprotein were analyzed with biochemical methods. Kidney index was calculated. Immunohistochemistry was employed to detect expressions of BMP-7, PKCα, ANG Ⅱ, CTGF and FN protein in renal tubules of all groups. The mRNA levels of BMP-7 and PKCα in renal cortex were examined by RT-PCR. Results Compared to control guoup, the expressions of PKCct protein and mRNA, ANG Ⅱ, CTGF and FN protein in renal tubular cells were increased remarkably to 94. 3% ,62.2% ,86. 2% ,93.6%, and 90. 8% in DG group. On the other hand, the protein and mRNA of BMP-7 decreased remarkably to 21% and 59.7% in DG. In DEG group,the expression of PKCct protein,PKCα mRNA,ANG Ⅱ ,and FN protein was down-regutated to 31.6% ,41.3% ,40. 2% ,54.7%, and 24%, respectively compared with that of DG;but the protein and mRNA of BMP-7 were up-regulated notably to 21.1% and 15.3%. The expression of BMP-7 protein was negatively correlated with PKCα,ANGⅡ ,CTGF and FN in DEG（r = -0.838, -0.885, -0. 829,and -0.931,P〈0.05 or P 〈0.01）. Conclusion Enalapril can diminish renal ANG Ⅱ level and up-regulatie PKCα and CTGF expression, then inhibit the expression of BMP-7 and therefore improve the damage in diabetic nephropathy.

关 键 词：糖尿病 骨形态发生蛋白-7 蛋白激酶CΑ 依那普利 

分 类 号：R332[医药卫生—人体生理学] R363[医药卫生—基础医学]