目的探讨曲美他嗪对冠状动脉微栓塞(CME)大鼠的心肌保护效果及机制。方法将SD大鼠随机分为对照组、模型组、干预组各12只。干预组术前连续3 d给予曲美他嗪10 mg/(kg·d)灌胃;模型组与干预组经左心室注射42μm微栓塞球建立CME模型,对照组经左心室注射等量生理盐水。术后6 h采用心脏超声检测心功能,免疫印迹法检测心肌组织Caspase-3及Caspase-8表达。结果与对照组比较,模型组与干预组左心室射血分数(LVEF)、心输出量(CO)及短轴缩短率(FS)均降低,左心室舒张末径(LVEDd)升高(P均〈0.05);与模型组比较,干预组LVEF、CO及FS均升高,LVEDd下降(P均〈0.05)。干预组心肌组织中Caspase-3与Caspase-8表达较对照组升高,较模型组降低(P均〈0.05)。结论曲美他嗪预处理可改善CME后心功能,该作用可能与其抑制Caspase-3与Caspase-8表达减少心肌细胞凋亡有关。
Objective To investigate the protective effects of trimetazidine on cardiac function after coronary microembolization( CME) in rats and the mechanism. Methods Thirty-six male SD rats were randomly divided into the control group,model group and trimetazidine intervention group( intervention group),12 rats in each group. The 42 μm microspheres were injected into the left ventricle to establish the CME model in rats of the model group and intervention group,and rats in the intervention group received trimetazidine 10 mg /( kg· d) for 3 days before the operation. For rats in the control group,the same dose of normal saline was substituted for microspheres. The cardiac function was detected by echocardiography,and the expression levels of caspase-3 and caspase-8 in the myocardial tissues were detected by Western blotting at 6 h after operation. Results Compared with the control group,the left ventricular ejection fraction( LVEF),cardiac output( CO) and fraction shortening( FS) were lower,whereas the left ventricular end-diastolic dimension( LVEDd)was higher in the model and intervention groups( all P〈0. 05). Compared with the model group,LVEF,CO and FS were increased but LVEDd was decreased in the intervention group( all P〈0. 05). The levels of caspase-3 and caspase-8 in the intervention group were higher than those of the control group,but lower than those of the model group( all P〈0. 05).Conclusion Trimetazidine pretreatment can significantly improve the cardiac function of rats after CME by attenuating apoptosis of myocardium through inhibiting the expression of caspase-3 and caspase-8.