曲美他嗪对实验性心肌缺血的保护作用

Protective effect of trimetazidine on rat with experimental myocardial ischemia

目的 :探讨曲美他嗪 (trimetazidine,TMZ)对心肌缺血缺氧的保护作用及其机制。 方法 :5 0只昆明种雄性小白鼠 ,随机分为三组 ,分别给予腹腔注射生理盐水稀释的 TMZ 5 mg/ kg、10 m g/ kg及等量生理盐水 ,连续 7d,第 6天起 ,按 2 0mg/ (kg· d)腹腔内注射异丙肾上腺素 ,连续 2 d,造成小鼠心肌坏死模型 ,制作光镜及电镜标本 ,观察心肌超微结构、血清心肌酶谱及心肌组织丙二醛 (MDA)、超氧化物歧化酶 (SOD)等的改变。 结果 :与对照组相比 ,两个治疗组心肌超微结构损害明显减轻 ,血清 CK及 L DH显著减低 (P<0 .0 5 ) ,心肌 MDA显著降低 (P<0 .0 1) ,SOD显著增高 (P<0 .0 1)。 结论 :TMZ能显著减轻异丙肾上腺素所致的心肌损害 ,对心肌缺血缺氧具有一定的保护作用 ,其机制可能与 TMZ能减少氧自由基产生等作用有关。

Objective: To investigate the protective effect of trimetazidine on experimental myocardial ischemia and its mechanism. Methods: Fifty mice received isoproterenol (20 mg·kg -1 ×2 d,ip) were divided into control and treatment groups. The myocyte ultrastructure,serum creatine phosphokinase (CK) activities and lactate dehydrogenase (LDH), myocardial malondialdehyde (MDA) and superoxide dismutase (SOD) were observed in 3 groups. Results: Compared with the controls,in 2 groups pretreated with trimetazidine (5 mg·kg -1 ·d -1 and 10 mg·kg -1 ·d -1 × 7 d, ip), the degree of myocardial damage were significantly reduced;the serum CK and LDH were lower;the myocardial MDA was lower;the myocardial SOD was higher. Conclusion: Trimetazidine can significantly reduce the degree of myocardial damage produced by isoproterenol;and it may play an important role in protecting ischemic myocardium, the mechanism may be associated with reduced oxygen free radical production.