阿托伐他汀对兔心肌缺血再灌注诱导细胞凋亡的影响

EFFECT OF ATORVASTATION ON MYOCARDIAL CELL APOPTOSIS DURING MYOCARDIAL ISCHEMIA/REPERFUSION IN RABBITS

目的探讨阿托伐他汀对兔心肌缺血再灌注诱导的细胞凋亡及Bcl-2、Bax蛋白表达的影响。方法30只雄性大白兔,随机分为假手术组(sham组)、缺血再灌注组(I/R组)及缺血再灌注加阿托伐他汀组(I/R+AT组)。采用结扎、开放兔冠状动脉的方法,制作兔心肌缺血再灌注模型(缺血40min,再灌注2h),采用原位末端标记法(TUNEL法)检测心肌细胞凋亡情况,采用免疫组织化学法检测心肌中Bcl-2、Bax蛋白的表达情况。结果①I/R组凋亡指数明显大于sham组(P<0.01),而I/R+AT组凋亡指数较I/R组显著减少(P<0.01)。②I/R组及I/R+AT组Bcl-2蛋白表达百分率显著高于sham组(均P<0.01),且I/R+AT组的Bcl-2蛋白表达也较I/R组明显上调(P<0.01);I/R组及I/R+AT组的Bax蛋白表达明显强于sham组(均P<0.01),但I/R+AT组的Bax蛋白表达弱于I/R组(P<0.01)。结论阿托伐他汀可以抑制心肌缺血再灌注诱导的细胞凋亡,减少心肌细胞凋亡数目,其机制可能与其上调心肌缺血再灌注时Bcl-2蛋白的表达、抑制Bax蛋白的表达有关。

Objective The purpose of this study was to explore the effect of atorvastatin on myocardial cell apoptosis induced by ischemia/reperfusion （I/R） in rabbits. Methods The myocardial I/R models of rabbits were established by means of obstructing and undoing left anterior descending arteries（ischemia for forty minute then reperfusion for two hours）. The 30 rabbits were randomly divided into sham group, ischemia/reperfusion group and ischemia/ reperfusion ＋ atorvastation group. The numbers of apoptotic cardiac muscle cells and the expression of Bcl-2 and Bax were respectively detected by means of TUNEL and immunohistochemical technique. Results （1）The apoptosis index （AI） of sham group was more than that in I/R group（ P d0.01）. The AI of I/R＋atorvastatin （I/R＋AT） group was obviously greater to that in sham group,but lower than I/R group（ P 〈0.01）. （2）Bcl-2 protein expression in I/R group is beyond that in sham group,and more up-regulation in I/R＋AT group（ P 〈0.01） The percentage rate of Bax protein expression in I/R group is significantly higher than that in sham group, and weaker than that in I/R＋AT group（ P 〈0.01）. Conclusion The present study revealed that atorvastatin could protect cardiac muscle cells from being injured induced by I/R. The mechanism might be by up-regulate of Bcl-2 protein expression and down-regulate of Bax protein expression.