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.doc

文档介绍：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
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作者:赵锡丽,徐蔚蔚,蒋国萍,刘小兰,戟芳
【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24h UAL、UN和Cr水平明显升高();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24h UAL、UN、Cr明显降低()。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();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()。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();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()。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。
【关键词】阿托伐他汀;糖尿病;大鼠;肾功能;TGFβ1/Smad信号通路
ABSTRACT: 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 24h 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. W
e 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 24h in model grou