HMG-CoA还原酶抑制剂阿托伐他汀对糖尿病大鼠肾脏的保护作用及其机制.docVIP

HMG-CoA还原酶抑制剂阿托伐他汀糖尿病大鼠肾保护 摘要: 探讨HMG-CoA还原酶抑制剂阿托伐他汀对糖尿病大鼠肾脏的保护作用及。 : 采用链脲佐菌素(streptozotocin, STZ) 腹腔注射法复制大鼠糖尿病(diabetesmellitus, DM)模型, 复制成功后随机分为模型对照组和阿托伐他汀治疗组, 另设正常对照组, 每组8只大鼠。于处理后的第1、2、4、8周分别检测各组大鼠24 h 尿白蛋白、尿素氮和肌酐水平。第8周, 取大鼠肾组织和外周血采用Western blot 检测大鼠肾脏组织中Smad2 蛋白表达水平 免疫组化检测大鼠肾脏组织中TGF-β1蛋白的表达情况,放射免疫法检测大鼠血清中层粘连蛋白(laminin, LN) 的表达水平。: 从第周开始, 模型对照组阿托伐他汀大鼠 24 h 尿白蛋白、尿素氮和肌酐水平阿托伐他汀处理降低糖尿病大鼠 24 h 尿白蛋白、尿素氮和肌酐水平模型对照组Smad2 蛋白水平阿托伐他汀可明显降低Smad2 蛋白表达水平 (P0.01)模型对照组 TGF-β1表达量明显增加与模型组相比，阿托伐他汀治疗组中TGF-β1 阳性细胞数量明显减少。放射免疫检测结果提示, 模型对照组经过阿托伐他汀治疗处理后, LN 表达水平明显降低 (P0.05)。: HMG-CoA还原酶抑制剂阿托伐他汀可能通过抑制TGF-β1 /Smad信号通路, 从而达到对糖尿病大鼠肾脏的保护作用。 关键词: 阿托伐他汀糖尿病大鼠 肾功能;TGF-β1 /Smad 信号通路HMG-CoA reducase inhibitor atorvastatin on nephridial tissue of diabetes rat and investigation of the related mechanism Zhao Xili, Xu Weiwei, Jang Guoping, Liu Xiaolan, Ji Fang ,Li Rong ,Yang Gangyi ABSTRACT: Objective: To investigate the kidney protection of hydroxy-methyl-glutaryl coenzyme A(HMG-CoA) reducase inhibitor atorvastatin and potential mechnisam. Methods: Intraperitoneal injection of streptozotocin(STZ) was employed to establish rats diabetesmellitus model. The rats were randomly separated into model group and atorvastatin treatment group after the establishment of diabetesmellitus model. Meanwhile, normal control group was set and 8 rats were in each group. The levels of urinary albumin(UAL), urea nitrogen (UN) and creatinine(Cr) during 24 h were recorded after the treatment, respectively. After 8-week treatment, the rats were sacrificed. Then, the nephridial tissue and peripheral blood(PB) were collected. The sera were separated from PB. Western blot was used to determine the expression level of Smad2 protein in the nephridial tissue. We employed immunohistochemistry to assay positive percent of TGF-β1 in the nephridial tissue. Radioimmunity(RI) was used to measure laminin(LN) product in the sera in groups. Results: From 1 week after the treatment, the levels of UAL, UN and Cr during 24 h in the model group a