曲美他嗪调控氧化应激大鼠慢性心力衰竭作用机制研究

Effects and Mechanism of Trimetazidine on Oxidative Stress in Rats with Chronic Heart Failure

目的研究曲美他嗪对腹主动脉缩窄诱导的慢性心力衰竭大鼠心肌氧化应激损伤的影响。方法将雄性SD大鼠随机分为4组,除对照组外,其他各组采用腹主动脉缩窄法制备心力衰竭模型,将模型大鼠随机分为模型组、曲美他嗪低剂量组和曲美他嗪高剂量组。治疗4周后行二维心脏超声检查、病理形态学观察、超微观察,并测定心肌组织起氧化歧化酶(SOD)。结果与模型组比较,曲美他嗪高剂量组大鼠左室射血分数(LVEF)、左心室短轴缩短率均提高;光镜和电镜下曲美他嗪高剂量组心肌损伤程度较模型组明显减轻。曲美他嗪高剂量组SOD的mRNA、蛋白以及血清表达水平与模型组比较,差异有统计学意义(P<0.05)。结论曲美他嗪能够改善心力衰竭大鼠心肌氧化相关指标、病理和超微结构,并且有改善大鼠心功能的趋势。

Objective To investigate the effects of trimetazidine on the injury of oxidative stress in rats with chronic heart failure（CHF）. Methods Male SD rats were randomly divided into blank control,model,low trimetazidine treated and high trimetazidine treated groups.Rats except for the blank control were abdominal aortic constricted.Four weeks later,echocardiography,real time PCR,serological and myocardial pathological examination were performed,SOD in myocardium was determined. Results Compared with the model rats,both LVPW and LVD of the rats in high dose of trimetazidine treated group were raised.The microscopic and electron microscopic examination showed that the myocardial injury in high dose of trimetazidine treated group were ameliorated compared with those in the model.The level of SOD showed significant difference among groups（P0.05）. Conclusion Trimetazidine can improve antioxidance,pathological change and ultrastructure of myocardium and enhance the cardiac function in rats with heart failure.