阿托伐他汀通过下调线粒体融合素2表达抑制大鼠心肌缺血再灌注后细胞凋亡  

Atorvastatin inhibits cardiomyocyte apoptosis via down-cegulation the expression mitofusin 2 after myocardial ischemia/reperfusion injury in rats

作　　者：周炜[1] 陈玲[1] 陈曼华[1] 

机构地区：[1]武汉市中心医院心内科,湖北武汉430014

出　　处：《细胞与分子免疫学杂志》2014年第4期388-390,395,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：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对大鼠心肌缺血再灌注(I/R)损伤后细胞凋亡及线粒体融合素2表达的影响。方法选取雄性SD大鼠32只,随机分为假手术组(sham),缺血再灌注组(I/R),阿托伐他汀1组(statin 1)和阿托伐他汀2组(statin 2),每组8只。Statin 1组术前7 d开始每日给予阿托伐他汀10 mg/(kg·d)灌胃,statin 2组药物剂量为40 mg/(kg·d),I/R组以等体积蒸馏水灌胃,随后制备心肌I/R损伤模型。各组于再灌注3 h后剪取心脏I/R损伤区域,脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测细胞凋亡,免疫印迹法检测磷酸化蛋白激酶B(p-Akt)的表达,免疫组化法检测线粒体融合素2的表达。结果与sham组相比,I/R组及statin 1组、statin 2组心肌细胞凋亡显著增加,p-Akt表达显著下降,线粒体融合素2表达显著增加(P<0.01);与I/R组相比,statin 1组、statin 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statin 1组变化更显著(P<0.05)。结论阿托伐他汀可抑制大鼠心肌缺血再灌注损伤后的细胞凋亡,其作用可能与抑制线粒体融合素2表达有关。Objective To investigate the effects of atorvastatin （statin for short） on cell apoptosis and the expression of mitofusin 2 （Mfn2） after myocardial ischemia/reperfusion （I/R） injury in rats. Methods A total of 32 male Sprague-Dawley rats were randomly divided into sham group, I/R group, statin group 1 and group 2, with 8 rats in each group. The rats in the two staUn groups were given atorvastatin 10 and 40 mg/（kg ~ d） daily since the 7th day before I/R injury, respectively. The rats in the I/R group were given distilled water instead. The I/R injury models were induced by the ligation of left anterior descending （LAD） artery for 30 minutes followed by recovering the blood stream. Three hours after reperfusion, the I/R injured areas of rat hearts were harvested, and cardiomyocyte apoptosis was assessed by in situ terminal deoxynucleotidyl transferase （TdT）-dUTP nick-end labeling （TUNEL）. Immunohistochemistry and Western blotting were respectively performed to determine the expressions of Mfn2 and phosphorylated Akt （p-Akt）. Results Three hours after reperfusion, the cardiomyocyte apoptosis and Mfn2 protein expression of the I/R and statin treatment groups remarkably increased, and p-Akt expression significantly decreased （P 〈0.01 ） as compared with those of the sham group. Compared with those of the I/R group, cardiomyocyte apoptosis and Mfn2 protein expression of statin groups were significantly reduced in a slightly dose-dependent manner （ P 〈 0. 05）, and p-Akt expression was obviously raised （ P 〈 0. 05）. Conclusion Atorvastatin can suppress cardiomyocyte apoptosis after I/R injury in rats, which may be related to the down-regulated expression of Mfn2.

关 键 词：阿托伐他汀 缺血再灌注 心肌细胞 凋亡 线粒体融合素2基因 

分 类 号：R541.4[医药卫生—心血管疾病] R392.33[医药卫生—内科学]