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目的:与倍他乐克进行对照,观察曲美他嗪(TMZ)对心肌梗死后心力衰竭大鼠的血流动力学参数、自由基代谢、心肌纤维化、血浆心钠素(ANP)和病理形态学方面(包括光镜和电镜)的影响,分析其产生作用的可能机制。方法:取雄性SD大鼠制成心肌梗死后心力衰竭模型,随机分为3组:心力衰竭对照组(S组);心力衰竭服用倍他乐克10mg·kg-1·d-1组(B组);心力衰竭服用TMZ10mg·kg-1·d-1组(T组)。每组8只,用药共6周。另设8只大鼠为假手术组(C组)。实验结束时进行血流动力学测定,血浆ANP、血清透明质酸(HA)、层黏蛋白(LN)、血浆和心肌组织匀浆中过氧化物歧化酶(SOD)、丙二醛(MDA)等指标,以及病理形态学的检测等。结果:用药6周后,与C组比较,S组、T组和B组左室收缩压(LVSP)下降,左室舒张末期压力(LVEDP)升高,±dp/dt降低;T组、B组与S组比较,LVSP上升,LVEDP下降,±dp/dt上升,T组和B组之间差异无统计学意义。S组、B组和T组的血浆SOD与C组相比,明显降低;S组的血浆MDA值与C组相比增高,T组血浆MDA值与其他3组比较降低。和C组相比,S、B和T组心肌组织的SOD均降低;B、T组的心肌SOD值较S组增高;S组的心肌MDA值较C组高。S、B和T组的血浆ANP值均显著高于C组,B组和T组明显低于S组。B、T、S组的血清HA值均比C组高,B、T组HA值与S组相比降低。光镜和电镜结果显示,T组和B组的心肌损害程度,较S组明显减轻。结论:TMZ可以改善心力衰竭大鼠的左室压力指标,改善自由基代谢,降低血浆ANP、HA值,改善心肌的病理和超微结构。
OBJECTIVE: To compare the effects of trimetazidine (TMZ) on hemodynamic parameters, free radical metabolism, myocardial fibrosis, plasma ANP and pathological changes in heart failure rats after myocardial infarction Morphology (including light and electron microscopy), analyze the possible mechanism of its role. Methods: Male SD rats were divided into 3 groups: heart failure control group (S group), heart failure group treated with metoprolol 10 mg · kg-1 · d-1 Group); TMZ10mg · kg-1 · d-1 group (T group). Each group of 8, a total of 6 weeks medication. Another 8 rats were sham operation group (C group). At the end of the experiment, hemodynamics, plasma ANP, serum hyaluronic acid (HA), laminin (LN), plasma superoxide dismutase (SOD) and malondialdehyde (MDA) And other indicators, as well as the detection of pathological morphology. Results: Compared with group C, the left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) increased and ± dp / dt decreased in group S, T and B after 6 weeks of treatment. Compared with S group, LVSP increased, LVEDP decreased and ± dp / dt increased. There was no significant difference between T group and B group. Plasma SOD in group S, B and T were significantly lower than that in group C; MDA in group S was higher than that in group C, while MDA in group T was lower than that in group C. Compared with group C, SOD in myocardial tissue of S, B and T groups were decreased; SOD in group B and T was higher than that in S group; MDA in group S was higher than that in C group. The plasma ANP values in S, B and T groups were significantly higher than those in C group, while those in B and T groups were significantly lower than those in S group. The serum HA values of B, T and S groups were higher than those of C group, while HA values of B and T groups were lower than those of S group. Light and electron microscopy showed that the degree of myocardial damage in group T and group B was significantly lower than that in group S. Conclusion: TMZ can improve left ventricular pressure in heart failure rats, improve free radical metabolism, decrease plasma ANP and HA, and improve myocardial pathology and ultrastructure.