曲美他嗪对大鼠缺血再灌注心肌线粒体的保护作用

Protective Effect of Trimetazidine on Rat Mitochondria with Myocardial Ischemia Reperfusion Injury

目的 探讨曲美他嗪对缺血再灌注损伤心肌线粒体的保护作用及其机制。方法 将5 0只SD雄性大鼠随机分为假手术组、生理盐水组和曲美他嗪组(5mg/kg组及10mg/kg组) 4组,假手术组只开胸,不结扎冠状动脉。余3组复制缺血再灌注损伤模型,缺血前分别静脉注射曲美他嗪(5或10mg/kg)及等量生理盐水,在缺血30min及再灌注4 0min时测定缺血再灌注损伤区心肌线粒体丙二醛、超氧化物歧化酶、谷胱甘肽、谷胱甘肽过氧化物酶及总钙浓度,并通过电镜观察心肌超微结构的改变。结果 与假手术组比较,生理盐水组及曲美他嗪组线粒体中的丙二醛及总钙显著增高,超氧化物歧化酶、谷胱甘肽及谷胱甘肽过氧化物酶显著降低。与生理盐水组比较,曲美他嗪组的丙二醛及总钙水平显著降低,超氧化物歧化酶、谷胱甘肽及谷胱甘肽过氧化物酶显著增高。电镜观察显示曲美他嗪组线粒体损伤较生理盐水组明显减轻。结论 以上提示曲美他嗪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谷胱甘肽含量及超氧化物歧化酶和谷胱甘肽过氧化物酶活性,以增强其抗氧化能力,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。

Aim To study the protective effect of trimetazidine (TMZ) on mitochondria of myocardial ischemia and ischemia 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 and 10 mg/kg). 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(RI). The level of malonaldehyole(MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px) and the accumulation of Ca 2+ in mitochondria of myocardial were detected at ischemia 30 min and reperfusion 40 min. The myocyte ultrastructure was also observed by electron microscope in 4 groups. Results Compared with the pseudooperation group, the MDA and total Ca 2+ were significantly higher and the SOD, GSH, GSH-Px were significantly lower in saline group and treated groups. Compared with the saline group, the MDA and total Ca 2+ was significantly lower and the SOD, GSH, GSH-Px were significantly higher in treated group. The ultrastructure changes of myocardium ulder electron microscope showed that the damage degree of mitochondria is slighter in TMZ treated groups than in saline group. Conclusions TMZ could significantly reduce the injury of lipid peroxidation of myocardial mitochondrial induced by ischemia and ischemia 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 mitochondria.