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  

Protective effects of HMG-CoA reducase inhibitor atorvastatin on nephridial tissues of diabetic rats and its related mechanism

作　　者：赵锡丽[1] 徐蔚蔚[1] 蒋国萍[1] 刘小兰[1] 戟芳[1] 

机构地区：[1]重庆医科大学附属第二医院内分泌科,重庆400010

出　　处：《西安交通大学学报（医学版）》2010年第4期459-462,共4页Journal of Xi’an Jiaotong University（Medical Sciences）

摘　　要：目的探讨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其可能的机制。方法采用链脲佐菌素(STZ)腹腔注射法复制大鼠糖尿病(DM)模型,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的24h尿白蛋白(UAL)、尿素氮(UN)和肌酐(Cr)水平。第8周,取大鼠肾组织和外周血。采用Western blot法检测大鼠肾脏组织中Smad2蛋白的表达;免疫组化法检测大鼠肾脏组织中TGF-β1蛋白的表达;放射免疫法检测血清中层粘连蛋白(LN)的表达。结果从第1周开始,与正常对照组比较,模型对照组和阿托伐他汀治疗组大鼠24hUAL、UN和Cr水平明显升高(P<0.01);而从第4周开始,与模型对照组比较,阿托伐他汀治疗组大鼠24hUAL、UN、Cr明显降低(P<0.01)。与正常对照组比较,模型对照组大鼠肾组织中Smad2蛋白水平虽有升高,但无统计学差异(P>0.05);而与模型对照组比较,阿托伐他汀治疗组Smad2蛋白表达明显降低(P<0.01)。与正常对照组比较,模型对照组大鼠肾组织中TGF-β1的表达量明显增加;而与模型对照组比较,阿托伐他汀治疗组TGF-β1阳性细胞数量则明显减少。模型对照组大鼠血清LN水平较正常对照组明显升高(P<0.01);而阿托伐他汀治疗组的LN表达水平较模型对照组明显降低(P<0.05)。结论 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。Objective To investigate the protective effects of hydroxy-methyl-glutaryl coenzyme A （HMG-CoA） reducase inhibitor atorvastatin on nephridial tissues of diabetic rats and its possible mechanism. Methods Streptozotocin （STZ） was injected intraperitoneally to establish rat diabetes mellitus （DM） model. Then the rats were randomized into model group and atorvastatin treatment group after the establishment of DM model. Meanwhile,normal control group was set and there were 8 rats in each group. The levels of urinary albumin （UAL）,urea nitrogen （UN） and creatinine （Cr） during 24 h were recorded respectively after the treatment. After 8-week treatment,the rats were sacrificed. Then,the nephridial tissues and peripheral blood （PB） samples were collected. The sera were separated from PB. Western blot was used to determine the level of Smad2 protein expression in the nephridial tissues. We employed immunohistochemistry to assay the percentage of TGF-β1 in the nephridial tissues and radioimmunity （RI） to measure laminin （LN） products in the sera in the groups. Results From the first week after treatment,the levels of UAL,UN and Cr during 24 h in model group and atorvastatin treatment group were significantly increased compared with those in the normal control group （P0.01）. From the fourth week after treatment,the levels of UAL,UN and Cr during 24 h were decreased significantly in atorvastatin treatment group compared with those in model group （P0.01）. Compared with the normal control group,Smad2 level in nephridial tissues of model control group was enhanced,but without significant differences （P0.05）. Atorvastatin treatment could decrease significantly the level of Smad2 expression in nephridial tissues compared with model control group （P0.01）. The expression of TGF-β1 in nephridial tissues in model control group was remarkably enhanced compared with that in the normal control group. The number of TGF-β1 positive cells was smaller in atorvastatin treatment group than

关 键 词：阿托伐他汀 糖尿病 大鼠 肾功能 TGF-Β1/SMAD信号通路 

分 类 号：R587.1[医药卫生—内分泌]