目的探讨曲美他嗪对急性心肌梗死(AMI)大鼠心室重构的抑制作用及其可能机制。方法取清洁级雄性健康SD大鼠60只,随机数字表法随机分为4组,每组各15只,即假手术组(C组),AMI模型组(M组),曲美他嗪低剂量组(L组),曲美他嗪高剂量组(H组)。C组只穿线不结扎,M、L、H三组均行开胸结扎左冠脉前降支方案,构建大鼠AMI模型,术后12 h开始L、H组分别给予曲美他嗪相应剂量灌胃1次/d(L组10 mg·kg~(-1)·d~(-1),H组20 mg·kg~(-1)·d~(-1)),喂养4 w。各组分别于术后24 h于眼动脉取血2 ml,测定血清肌酸激酶(CPK),丙二醛(MDA),超氧化物歧化酶(T-SOD),游离脂肪酸(FFA)。术后4 w观察各组心肌肥厚指数变化和各组心肌胶原(MC)含量变化,获取心肌细胞结构及心肌胶原纤维增生的有关图像数据。结果术后24 h各组血清CPK、血清MDA均较C组升高(P均<0.05),而血清T-SOD较C组则下降(P均<0.05),其中M组变化最显著;L、H组血清CPK、血清MDA较M组减低,而血清T-SOD则升高(P均<0.05),且H组变化更为显著(P<0.05)。另外,M组血清FFA较C组显著升高(P<0.05),L、H组较M组则显著降低(P<0.05)。术后4 w,与C组比较,M、L、H组心肌肥厚指数均增大(P均<0.01),而M组增大最明显;与M组比较,L、H组则明显下降(P<0.05)。术后4 w,与C组比较,M、L、H组MC含量均明显升高(P均<0.05),而M组升高最显著(P<0.001),与M组比较,L、H组则显著下降(P<0.05),且呈剂量依赖性。MC含量与血清CPK活力(r=0.85,P<0.001)和MDA含量(r=0.76,P<0.001)呈正相关。光镜MASSON染色和透射电镜结果显示:M组心肌及线粒体结构破坏最严重,且胶原纤维堆积明显,L、H组较M组改善。结论曲美他嗪对大鼠AMI后心室重构有抑制效果,缓解心肌纤维化。且这可能与其优化心肌代谢、减轻细胞缺血损伤后氧化应激反应、保护线粒体超微结构从而减少心肌细胞损伤作用相关。 Objective To investigate the inhibitory effect of trimetazidine on ventricular remodeling in rats with acute myocardial infarction (AMI) and its possible mechanism. Methods Sixty clean male Sprague-Dawley rats were randomly divided into four groups (n = 15 each): sham operation group (C group), AMI model group (M group), trimetazidine low Dose group (L group), trimetazidine high-dose group (H group). Group C was threaded only and did not ligate. M, L and H groups underwent thoracotomy for ligation of the left anterior descending coronary artery. AMI model was established in rats. At 12 hours after operation, L and H groups were given corresponding doses of trimetazidine Gavage once a day (L group, 10 mg · kg -1 · d -1, H group, 20 mg · kg -1 · d -1), feeding 4 w. Serum creatine kinase (CPK), malondialdehyde (MDA), superoxide dismutase (T-SOD) and free fatty acid (FFA) were measured in 2 ml blood in the ophthalmic artery 24 hours after operation. After 4 weeks, changes of myocardial hypertrophy index and changes of myocardial collagen (MC) in each group were observed, and the related image data of myocardial cell structure and myocardial collagen fibrosis were obtained. Results The levels of serum CPK and MDA in serum of all the groups at 24 h after operation were significantly higher than those in C group (all P <0.05), while those of serum T-SOD were lower than those in C group (all P <0.05) (P <0.05). The serum CPK and serum MDA in group H were lower than those in group M and serum T-SOD (all P <0.05), and the changes in group H were more significant (P <0.05). In addition, serum FFA in M ​​group was significantly higher than that in C group (P <0.05), and L and H groups were significantly lower than M group (P <0.05). Compared with group C, myocardial hypertrophy index in M, L and H groups increased at 4 w after operation (P <0.01), while M group increased most obviously. Compared with M group, L and H groups decreased significantly P <0.05). Compared with group C, the MC contents in M, L and H groups were significantly increased at 4 w after operation (P <0.05), while the M group increased most significantly (P <0.001). Compared with M group, L and H Group was significantly decreased (P <0.05), and in a dose-dependent manner. MC content was positively correlated with serum CPK activity (r = 0.85, P <0.001) and MDA content (r = 0.76, P <0.001). Light microscopy MASSON staining and transmission electron microscopy results showed that: M group myocardial and mitochondrial structure most severely damaged, and accumulation of collagen fibers obvious, L, H group improved compared with M group. Conclusion Trimetazidine can inhibit ventricular remodeling after myocardial infarction in rats and relieve myocardial fibrosis. And this may be related to its optimization of myocardial metabolism, reduce oxidative stress response after ischemia, protect the mitochondrial ultrastructure and thus reduce the role of myocardial cell injury.