AIM:To observe the myocardial protective effects of trimetazidine on myocardiai infarction (MI) in Sprague - Dawley (SD) rats. METHODS; Ninety SD rats were randomly assigned to 3 groups (n =30 each) ; myocardial infarction group ( MI group), MI + trimetazidine group ( MT group) and sham group (S group). By permanently ligating the left anterior descending artery, the MI model was set up in the rats in MI group and MT grotfp. Before and after setting up the MI model, normal saline was given to the rats in MI and S group by gavage. On the other hand, trimetazidine (3 mg/kg,twice per day) was given to the rats in MT group by gavage. At 8 h, 24 h and 48 h after applying trimetazidine, the serum level of cardiac troponin I ( cTnl) was measured. At the 1 st week, 2nd week and 4th week after treated with trimetazidine , the size of myocardial infarction, the maximum rising rate of the left ventricular systolic pressure ( + dp/dtmax ) and the maximum descending rate of the left ventricular diastolic pressure ( - dp/dtmax) were measured. Also at the 1st week after applying trimetazidine, the cardiomyocyte apoptotic index was detected. RESULTS: Compared with MI group 2 weeks after applying trimetazidine, + dp/dtmax significantly increased in MT group [ (8 101 ±990) mmHg/s vs (5 868 ± 1 302) mmHg/s, P<0. 01 ], and -dp/dt^ also significantly increased in MT group [ (6 514 ± 1 558) mmHg/s vs (4 750 ± 1 463) mmHg/s, P < 0. 01 ]. Four weeks after applying trimetazidine, + dp/dtmax significantly increased in MT group [(7 629±1 181) mmHg/s is (5620±454) mmHg/s, P<0.01], and - dp/dtmax also significantly increased in MT group [ (5 883 ± 1 379) mmHg/s vs (4 256 ±731) mmHg/s, P <0. 01 ]. At 8 h and 48 h after applying trimetazidine, no statistically significant difference (P >0. 05) of serum cTnl between MI group and MT group was observed. However, at 24 h after applying trimetazidine, the serum level of cTnl decreased in MT group [ (22. 7 ± 14.9) ng/L] as compared with MI group [ (42.3 ± 16.2) u,g/L, P <0.01 ]. Aditionally, trimetazidine significantly decreased the infarction size of myocardium in MT group ( 0.248 ± 0.052) as compared with MI group (0. 362 ± 0.082, P < 0.01). CONCLUSION: Trimetazidine has short - term cardioprotective effects on the rats with acute MI by improving myocardial systolic and diastolic functions, reducing infarct size and inhibiting apoptosis.%目的:探讨曲美他嗪对大鼠心肌梗死心脏的保护作用及其部分作用机制.方法:90只SPF级SD大鼠随机分为3组:假手术组(n=30)、心肌梗死组(n=30)和曲美他嗪治疗组(n=30).心肌梗死组和曲美他嗪治疗组在高位结扎左冠状动脉前降支,制成心肌梗死模型.假手术组及心肌梗死组在术前灌胃给予生理盐水,曲美他嗪组灌胃给予曲美他嗪(3 mg/kg,每天2次),连续治疗1周、2周和4周.冠脉结扎后8 h、24 h和48 h检测血清心肌肌钙蛋白I浓度.在治疗后1周、2周和4周后测量平均动脉压、心率、收缩期心室压力最大上升速率(+dp/dtmax)及舒张期左室压力最大下降速率(-dp/dtmax),并检测心肌梗死面积,TUNEL法检测心肌细胞凋亡指数.结果:在连续给药2周及4周后曲美他嗪组与心肌梗死组相比,能显著改善大鼠的心脏收缩功能[第2周:+dp/dtmax (8 101±990)mmHg/s vs (5 868±1 302)mmHg/s; 第4周:+dp/dtmax (7 629±1 181) mmHg/s vs (5 620±454) mmHg/s]及舒张功能[第2周:-dp/dtmax (6 514±1 558) mmHg/s vs (4 750±1 463) mmHg/s;第4周:(5 883±1 379) mmHg/s vs (4 256±731) mmHg/s](均P＜0.01),不影响心率及平均动脉压(P＞0.05); 曲美他嗪可降低大鼠心肌梗死后24 h血清心肌肌钙蛋白I水平(P＜0.01),减少大鼠心肌梗死面积(P＜0.01),并抑制心肌缺血损伤区的心肌细胞凋亡(P＜0.01).结论:曲美他嗪对心肌梗死后大鼠具有明确的心脏保护作用,抑制心肌梗死后缺血损伤区细胞凋亡是其心肌保护作用的机制之一.
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