目的探讨曲美他嗪对巴马系小型猪急性冠状动脉微栓塞(CME)后心肌细胞凋亡的影响及意义。方法健康巴马系小型猪随机分为假手术组、CME组和CME+曲美他嗪组,每组5只。采用经皮冠状动脉介入法,于左前降支中远端经微导管注入微栓塞球建立CME模型;假手术组注入等量生理盐水;CME+曲美他嗪组术前30min经耳缘静脉注入曲美他嗪。术后9 h采用心脏超声检测心功能,TUNEL染色检测心肌细胞凋亡,Western blot检测活化Caspase-8和Caspase-3表达水平。结果与假手术组相比,CME组左心室射血分数(LVEF)、左心室短轴缩短率(FS)及心排血量(CO)下降,左心室舒张期末内径(LVEDd)增加(P〈0.05);与CME组相比,CME+曲美他嗪组心功能明显改善(P〈0.05)。与假手术组相比,CME组心肌细胞凋亡率、活化Caspase-8及Caspase-3含量显著增加(P〈0.05);与CME组相比,CME+曲美他嗪组心肌细胞凋亡率、活化Caspae-8及Caspase-3含量明显减少(P〈0.05)。结论曲美他嗪预处理可明显减少CME后心肌细胞凋亡并改善心功能,其机制可能是阻断心肌细胞Caspase-8介导的死亡受体凋亡途径的激活。
Aim To explore the effect of trimetazidine on cardiomyocyte apoptosis after coronary microembolization(CME) in swine.Methods Fifteen swine were randomly and equally assigned into sham-operated(control)group,CME group and trimetazidine group.CME was induced by injection of microspheres selectively into left anterior descending artery; for control group,the same dose of normal saline was substituted for microspheres; and those in trimetazidine group were pretreated with trimetazidine 30 min before microspheres injection.Cardiac function was assessed by echocardiography,cardiomyocyte apoptosis was detected by TUNEL staining,and the expression levels of caspase-8 and caspase-3 were measured by Western blot 9 h after operation.Results Compared with sham-operated group,cardiac function was significantly decreased in CME group(P〈0.05); However,cardiac function was significantly improved in trimetazidine group compared with CME group(P〈0.05).Compared with control group,myocardial apoptosis rate and the levels of activated caspase-8 and-3 increased significantly in CME group(P〈0.05).Again,these effects were ameliorated by trimetazidine(P〈0.05).Conclusion Trimetazidine pretreatment suppressed post-CME myocardial apoptosis and improved cardiac function probably by inhibiting myocardial death receptor-mediated apoptotic pathway.