缺血再灌注心肌细胞凋亡及药物干预

APOPTOSIS OF CARDIAC MYOCYTES IN ISCHEMIC AND REPERFUSED RATS AND THE INTERFERENCE OF DRUG

目的 :研究葛根素和维拉帕米对大鼠缺血再灌注心肌细胞凋亡的影响。方法 :对 5 6只成年Wistar雄性大鼠建立冠状动脉左前降支 (LAD)缺血再灌注模型 ,其中 3 2只大鼠在缺血前及再灌注前给予维拉帕米和葛根素进行干预治疗 ,观察大鼠缺血再灌注心肌细胞凋亡及相关基因Bcl 2和Bax的表达情况以及维拉帕米和葛根素对其影响。采用末端标记法 (TUNEL)进行细胞凋亡检测 ;应用免疫组化的方法检测Bcl 2和Bax的表达。结果 :假手术组及单纯缺血组凋亡细胞无明显增多 ,而缺血再灌注组凋亡细胞明显增多 (P <0 .0 0 1) ;在缺血前及再灌注前给予维拉帕米治疗均可减少细胞凋亡的数量 (P <0 .0 0 1) ;在再灌注前给予葛根素治疗也可减少因再灌注引起的细胞凋亡 (P =0 .0 0 3 )。Bcl 2和Bax的表达在单纯缺血组、再灌注组以及药物治疗组均增加。结论 :在缺血再灌注后可见心肌细胞凋亡发生 ,再灌注可加速细胞凋亡的发生 ;维拉帕米和葛根素可抑制心肌细胞凋亡 ;Bcl 2和Bax在受到缺血刺激后表达增加。

OBJECTIVE:To study the effects of verapamil and purarin on apoptosis of cardiac myocytes in ischemic and reperfused rats. METHODS:Ischemic and reperfused model of 56 male adult rats was established by LAD occlusion, among them 32 rats were pre treated with verapamil and puerarin. Then apoptosis of cardiac myocytes, Bcl 2 and Bax related genes and influence of verapamil and puerarin were observed. Apoptotic myocytes were detected with TUNEL; Bcl 2 and Bax were detected with immunhisochemistry. RESULTS:Apoptotic myocytes were not increased in ischemia only group but significantly increased in ischemic and reperfused group ( P <0.001); the amount of apoptotic myocytes may be reduced by treatment with verapamil before ischemia or before reperfusion ( P <0.001) and may also be reduced by treatment with puerarin before reperfusion ( P <0.003). The expression of Bcl 2 and Bax were increased in ischemic, reperfused, and pretreatment groups. CONCLUSION:Apoptosis of cardiac myocytes were observed after ischemic and reperfusion. The process can be accelerated by perfusion and inhibited by pre-treatment with verapamil or puerarin. The expression of Bcl 2 and Bax were increased by ischemic stimulation.