阿托伐他汀下调大鼠心肌梗死后线粒体融合素2表达和细胞凋亡  

Atorvastatin down regulates mitofusin 2 gene expression and cell apoptosis

作　　者：周炜[1] 陈玲[1] 周逸[1] 陈曼华[1] 

机构地区：[1]武汉市中心医院心血管内科,湖北武汉430014

出　　处：《基础医学与临床》2014年第2期168-171,共4页Basic and Clinical Medicine

基　　金：国家自然科学基金(81300214);湖北省自然科学基金(2013CFB378);武汉市卫生局临床医学科研项目(WX12B03);武汉市科技局关键技术攻关计划(2013060602010256)

摘　　要：目的研究阿托伐他汀通过下调线粒体融合素2表达抑制大鼠心肌梗死后细胞凋亡。方法雄性SD大鼠48只,随机分为假手术组(sham),心肌梗死组(MI),阿托伐他汀1组(statin 1)和2组(statin 2),每组12只。分别于术前7天开始每日灌胃,给予阿托伐他汀10和40 mg/kg,MI组以蒸馏水灌胃,随后结扎大鼠前降支建立心肌梗死模型。术后24 h用TUNEL法检测心肌细胞凋亡,免疫组化法检测线粒体融合素2表达,免疫印迹法检测磷酸化蛋白激酶B(p-Akt)表达。结果与sham组相比,MI组心肌细胞凋亡显著增加,线粒体融合素2表达显著增加,p-Akt表达显著下降(P<0.01);与MI组相比,statin 1和2组心肌细胞凋亡和线粒体融合素2表达均显著降低(P<0.05),而p-Akt表达显著增高(P<0.05),且statin 2组较1组变化更显著(P<0.05)。结论阿托伐他汀可抑制大鼠心肌梗死后的细胞凋亡,其作用可能与下调线粒体融合素2表达有关。Objective To investigate the effects of atorvastatin on myocardial apoptosis and mitofusin 2 （Mfn2） ex- pression after acute myocardial infartion （MI） in rats. Methods A total of 48 male Sprague-Dawley rats were ran- domly divided into sham-operated group, myocardial infartion（MI） group, statin group 1 and group 2. The rats in the two statin groups were given atorvastatin 10 mg/kg or 40 mg/kg daily. The rats in the M1 and statin groups acute my- ocardial infartion. 24 hours after operation were induced the MI area of rat hearts was collected, and myocardial apop- tosis was assessed by in situ terminal deoxynucleotidyl transferase （TdT）-dUTP nick-end labeling（TUNEL staining）. Immunohistochemistry staining and western blotting were performed to measure the expression of Mfn 2 and phospho- rylated Akt（p-Akt）. Results 24 hours after operation, the myocardial apoptosis and Mfn2 protein expression of the MI groups remarkably increased （P 〈 0. 01 ）. While myocardial apoptosis and Mfn2 protein expression in statin groups significantly decreased with a slightly dose-dependent manner（P 〈 0. 05）. Conclusions Atorvastatin attenuates myo- cardium apoptosis after acute myocardial infarction in rats, which may be explained by down-regulated expression of mitofusin 2.

关 键 词：阿托伐他汀 心肌梗死 凋亡 线粒体融合素2基因 

分 类 号：R542.22[医药卫生—心血管疾病]