曲美他嗪对大鼠缺血再灌注心肌线粒体的保护作用

目的探讨曲美他嗪(trimetazidine,TMZ)对缺血再灌注损伤(RI)心肌线粒体的保护作用及其机制.方法50只雄性SD大鼠随机分为假手术组、等渗盐水组和药物组(TMZ 5 mg/kg组及TMZ 10 mg/kg组)共四组,假手术组只剖胸,不结扎冠状动脉.余三组制作RI模型,缺血前分别静脉注射TMZ(5 mg/kg或10 mg/kg)或等量等渗盐水,在缺血30 min及再灌注40 min时测定RI区心肌线粒体丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-PX)及总钙浓度,并通过电镜观察心肌超微结构改变.结果与假手术组相比,等渗盐水组及药物组线粒体中的MDA及总钙显著增高(P＜0.01),SOD、GSH及GSH-PX显著降低(均P＜0.01);与等渗盐水组比较,药物组的MDA及总钙水平显著降低(P＜0.05,P＜0.01),SOD、GSH及GSH-PX显著增高(P＜0.05,P＜0.01).结论TMZ能减轻缺血再灌注心肌线粒体的脂质过氧化损伤,其机制可能是通过提高线粒体内GSH含量及SOD、GSH-PX活性,增强其抗氧化能力,并通过减轻线粒体内钙聚积在细胞水平提供心肌保护作用.

Protective effects of trimetazidine on mitochondral in myocardial ischemia reperfusion rats

Objective:To study the protective effects of trimetazidine (TMZ) on mitochondrial in myocardial ischemia reperfusion rats and its mechanism. Methods: Fifty SD rats were randomly divided into four groups; the pseudooperation group, the saline group and two TMZ treated groups(5 mg/kg and 10 mg/kg). In the pseudooperation group, the coronary artery was not ligated, but the chest was opened. Other groups were subjected to myocardial ischemia reperfusion injury. The serum level of mal onaldehyole ( MDA ) , superoxide dismutase ( SOD ) , glutathione ( GSH ) , glutathione peroxidase (GSH-PX) and the accumulation of Ca2+ in myocardial mitochondrial were detected at the time of 30 min ischemia and 40 min reperfusion. The myocyte ultrastnicture was also observed by electron microscope in the four groups. Results: Compared with the pseudooperation group, the MDA and total Ca2+ were significantly higher and the SOD, GSH, and GSH-PX were significantly lower in saline group and treatment groups. Compared with the saline group, the MDA and total Ca2+ was significantly lower and the SOD, GSH, and GSH-PX were significantly higher in the treatment groups. Conclusion: TMZ could significantly reduce lipid peroxidation in myocardial mitochondrial induced by ischemia and ische-mia-reperfusion. The mechanism may be that TMZ could increase the content of GSH and the acvitity of SOD and GSH-PX, and enhance its antioxidant production. TMZ could protect the cardiac cells by reducing calcium overload in myocardial mitochondrial.