曲美他嗪对大鼠心肌缺血再灌注损伤的保护作用

Protective effect of trimetazidine on rats myocardial ischemia reperfusion injury

目的 :探讨曲美他嗪 (trimetazidine ,TMZ)对心肌缺血再灌注损伤 (RI)的保护作用及其机制。 方法 :5 0只SD雄性大鼠随机分为假手术组、生理盐水组和药物组 (TMZ 5或 10mg/kg) ,共 4组 ,假手术组只开胸 ,不结扎冠脉。余 3组制作RI模型 ,缺血前分别静脉注射TMZ(5或 10mg/kg)及等量生理盐水 ,在缺血 30min及再灌注 4 0min时分别测定血清肌酸磷酸激酶 (CK) ,再灌注 4 0min时测定RI区心肌丙二醛 (MDA)、超氧化物歧化酶 (SOD)、谷胱甘肽 (GSH)及谷胱甘肽过氧化物酶(GSH Px)等变化。 结果 :药物组在缺血 30min时及再灌注 4 0min时的血清CK较生理盐水组显著降低。与假手术组相比 ,生理盐水组及药物组的MDA显著增高 ,SOD、GSH及GSH Px显著降低 ;与生理盐水组比较 ,药物组的MDA显著降低 ,SOD、GSH及GSH Px显著增高。 结论 :TMZ能抑制心肌细胞缺血及再灌注时心肌酶的漏出 ,对心肌缺血及缺血再灌注损伤具有一定的保护作用。其机制可能是通过提高体内自由基清除剂GSH的含量及SOD、GSH Px的活力 。

Objective:To study the protective effect of trimetazidine(TMZ) on myocardial ischemia and reperfusion injury and its mechanism.Methods:Totally 50 SD rats were randomly divided into 4 groups:the pseudooperation group,the saline group and the TMZ treated groups(5 mg·kg -1 and 10 mg·kg -1 ).In the pseudooperation group the coronary artery was not ligated but the chest was opened,the other groups were the model of myocardial ischemia reperfusion injury.The level of serum creatine phosphokinase(CK) was detected at ischemia 30 min and reperfusion 40 min; The reperfusion injury myocardial malonaldehyole(MDA),superoxide dismutase(SOD),glutathione(GSH),glutathione peroxidase(GSH Px) were detected at reperfusion 40 min.Results:The level of CK was significantly lower in treated groups than in saline group both at ischemia 30 min and reperfusion 40 min;Compared with the pseudooperation group,the MDA was higher and the SOD,GSH and GSH Px were significantly lower in saline group and treated groups;Compared with the saline group,the MDA was higher and the SOD,GSH and GSH Px were significantly lower in treated groups.Conclusion:TMZ can inhibit enzyme leaking from the ischemia reperfusion myocardial cells,and protect the cardiac cells against ischemia reperfusion injury to some extent.The mechanism may be that TMZ can reduce the injury of lipid peroxidation and harmful metabolites to cardiac cell membrane by increasing the content of GSH,the free radical cleaner,and enhancing the activity of SOD and GSH Px.