缬沙坦对糖尿病大鼠足细胞保护作用的研究  被引量:1

Protective effect of valsartan on the podocytes of diabetic rats

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作  者:黄珍珍[1] 任伟[1] 王艳[1] 陈玉米[1] 叶山东[2] 邢燕[2] 胡闻[3] 

机构地区:[1]安徽医科大学附属省立医院肾内科,合肥230001 [2]安徽医科大学附属省立医院内分泌科,合肥230001 [3]安徽医科大学附属省立医院病理科,合肥230001

出  处:《安徽医科大学学报》2016年第1期73-77,共5页Acta Universitatis Medicinalis Anhui

基  金:安徽省年度重点科研项目(编号:12070403059)

摘  要:目的观察缬沙坦对糖尿病大鼠足细胞相关蛋白表达的影响,探讨肾素-血管紧张素系统(RAS)抑制剂保护糖尿病大鼠足细胞的机制。方法将36只健康雄性SD大鼠随机分为正常对照组和实验组。实验组使用链脲佐菌素(STZ)诱导建立糖尿病大鼠模型,随机将其分为糖尿病模型组、缬沙坦干预组。8周后分别检测各组大鼠糖化血红蛋白(Hb A1C)、尿白蛋白(UALB)、尿肌酐(UCR)、尿视黄醇结合蛋白(URBP)及肾脏肥大指数(KI)的变化,并计算尿白蛋白/肌酐(UACR)和尿视黄醇结合蛋白/肌酐(UBCR),每周监测各组血糖(BG);8周后利用光镜及电镜观察大鼠肾脏病理及足细胞形态变化;采用免疫组化、RT-PCR法分别检测肾组织Podocin蛋白和mRNA的表达。结果与正常对照组比较,糖尿病模型组和缬沙坦干预组糖尿病大鼠BG、Hb A1C、UACR、UBCR、KI均明显增高(P<0.01),肾脏皮质Podocin mRNA及肾组织Podocin蛋白表达水平均显著降低(P<0.01),肾脏肾小球体积增大,基底膜增厚,足细胞病变较重;与糖尿病模型组比较,缬沙坦干预组除BG及Hb A1C外,UACR、UBCR、KI均明显降低(P<0.01),肾脏皮质Podocin mRNA及肾组织Podocin蛋白表达水平增高(P<0.01),肾小球、小管间质、基底膜及足细胞的病理损伤减轻。结论缬沙坦对糖尿病大鼠肾脏足细胞有明显的保护作用,其部分机制可能是通过上调肾组织Podocin mRNA和蛋白表达。Objective To observe the effects of valsartan on the podocin expression in podocytes of diabetic rats and to explore the mechanism of valsartan ( an angiotensin Ⅱ receptor antagonist) on the kidney of diabetic rats. Methods Thirty-six healthy Sprague-Dawley (SD) rats were randomly divided into normal control group and ex- perimental group. Rats in experimental group were given streptozocin (STZ) by intrapetitoneal injection to establish animal models of diabetes, then the rat models were randomly divided into DN group and valsartan-treated group . Furthermore, after 8 weeks, glycated hemoglobin ( HbAlC ), urinary albumin ( UALB ), urinary creatinine ( UCR), urinary retinol binding protein (URBP) and kidney hypertrophy index (KI) were determined to eliminate the impact of urine volume,and the parameters mentioned above were expressed as UALB/UCR(UACR) ,URBP/UCR( UB- CR). Blood glucose was measured weekly in all groups. Podocin protein and mRNA expression in renal tissues were measured by immunohistochemistry and RT-PCR. The renal histomorphology and the structural change of podocytes were observed through optic microscope and electron microscope. Results Compared to the normal control group, BG, UACR, UBCR, HbA1C, KI were markedly higher in DN group and valsartan-treated group (P 〈 0. 01 ). The renal Podocin protein and mRNA expression of kidney were significantly decreased (P 〈 0. 01 ). The renal patho- logical lesions of rats in DN group were obvious. Compared to DN group, except for BG and HbA1C, UACR, UB- CR, KI were significantly decreased in valsartan-treated group (P 〈 0. 01 ). The renal Podocin protein and mRNA expression of kidney were significantly raised ( P 〈 0.01 ). The pathomorphologica change in golmerulus, tubules and podocytes showed a better improvement in valsartan-treated group. Conclusion Valsartan exerts the protective effect on the podocytes in diabetic rats, and the mechanism may be achieved by the up-regulatied expression of

关 键 词:糖尿病肾病 足细胞 PODOCIN 缬沙坦 

分 类 号:R587.24[医药卫生—内分泌]

 

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