盐酸贝那普利对糖尿病大鼠肾脏足细胞及其蛋白nephrin表达的影响

The effects of hydrochloride Benazepril on podocyte nephrin protein expression in diabetic rats

目的观察盐酸贝那普利对糖尿病大鼠足细胞及其nephrin蛋白表达的影响,初步探讨其对糖尿病大鼠肾脏保护作用及其可能的机制。方法将健康雄性SD大鼠随机分为正常对照(NC组)和实验组。实验组通过一次性腹腔注射链脲佐菌素建立糖尿病大鼠模型,造模成功后,随机分为糖尿病对照组(DM组)和贝那普利干预组(DT组),DT组予以盐酸贝那普利10 mg.kg-1.d-1,混悬液灌胃。NC、DM组予以等量0.9%氯化钠注射溶液相应时间灌胃。每周监测各组大鼠尾外周血血糖。4周后,检测糖化血红蛋白(HbA1c)及尿液中nephrin蛋白、白蛋白(ALB)及视黄醇结合蛋白(RBP)。处死大鼠留取肾脏标本,在电镜下观察肾脏组织形态学及足细胞超微结构的变化,采用免疫组织化学方法检测肾组织nephrin蛋白的表达水平。结果造膜4周后,DM和DT组的HbA1c、肾脏肥大指数、尿nephrin/肌酐(Cr)、尿ALB/Cr、尿RBP/Cr与NC组相比,差异有统计学意义(P<0.05),DM和DT组与NC组nephrin表达水平差异有统计学意义(P<0.05),电镜下糖尿病大鼠组与NC组相比肾组织病变明显。与DM组比较,DT组除血糖和HbA1c水平外,其余各项指标二组之间均差异有统计学意义(P<0.05),肾组织病理改变亦明显减轻。结论贝那普利通过上调nephrin表达水平改善修复受损足细胞,减少足细胞脱落,从而减少糖尿病大鼠蛋白尿,对糖尿病肾病发挥保护作用。

Objective To observe effects of hydrochloride benazepril on podocyte nephrin protein expression in diabetic rats and investigate its protective effects on the kidney of rats and its possible mechanism.Methods Sprague-Dawley（SD） rats were assigned to normal control and model group.The diabetes model was established by a single injection of streptozotoin（STZ）,randomly divided into diabetic nephropathy（DM group） and benazepril intervention group（DT group）.DT group received benazepril hydrochloride.NC,DM group was gived the equal saline in a appropriate time.Peripheral blood glucose was tested weekly in all groups.At the end of the 4th week,blood glucose,HbA1c,urinary nephrin protein,urinary albumin,and urinary retinol-binding protein were tested.The renal tissues of diabetic rats were obtained after the rats sacrifice to observe the structure changes and morphological changes in kidney podocytes under electron microscope and measure nephrin protein expression by immunohistochemistry.Results At the end of the 4th week,all indexes measured above and the relative kidney index were markedly increased in group DM when compared with those in group DT（P0.05）,in comparison with those in group NC,DM and DT group was were markedly increased in nephrin expression levels（P0.05）,the renal pathological lesions of rats in group DM were obvious.Benazepril treatment could significantly decrease the parameters above（P0.01） and lessen the renal pathological lesions in comparison with those in group DM except the blood glucose and HbA1c.Conclusion Benazepril exerts reno-protective effect via increasing nephrin expression to repair the damaged foot cells and reducing podocyte loss to decrease proteinuria of diabetic rats.