曲美他嗪对心力衰竭犬氧化应激状态的影响  

Effects of trimetazidine on oxidative stress in dogs with heart failure

作　　者：霍红 王凤荣[1] Huo Hong;Wang Fengrong(Liaoning University of Traditional Chinese Medicine,Shenyang 110032)

机构地区：[1]辽宁中医药大学,沈阳110032

出　　处：《安徽医科大学学报》2018年第6期908-912,共5页Acta Universitatis Medicinalis Anhui

基　　金：黑龙江省卫生计生委科研课题(编号:2017-469)

摘　　要：目的研究曲美他嗪对心衰犬心肌细胞氧化应激状态及形态结构的影响。方法采用快速起搏心室构建心衰犬模型,将模型制造成功的15只犬随机分为3组:假手术组、模型组、曲美他嗪组[灌服曲美他嗪5 mg/(kg·d)],连续6周。实验结束后留取犬左心室心肌组织,应用硫代巴比妥法测定丙二醛(MDA),黄嘌呤氧化酶法测定超氧化物岐化酶(SOD),RT-PCR技术测定丙酮酸脱氢酶(PDH)mRNA表达,行病理形态学及心肌超微结构观察。结果曲美他嗪组犬心肌组织中SOD活性升高,MDA表达下降。曲美他嗪治疗后PDH mRNA表达上调,高于模型组,差异有统计学意义(P<0.05)。光镜和电镜下观察曲美他嗪组心肌损伤程度低于模型组,差异有统计学意义(P<0.05)。结论曲美他嗪能够改善心衰犬心肌细胞氧化应激状态,其机制可能与曲美他嗪减少烟酰胺腺嘌呤二核苷酸(NADH)生成,间接提高PDH mRNA的表达,提高葡萄糖氧化,抑制脂质过氧化反应,改善心肌能量代谢有关。Objective To investigate the effect of trimetazidine on oxidative stress and morphological structure of cardiomyocytes in dogs with heart failure. Methods A model of heart failure was established by rapid pacing,and 15 dogs were randomly divided into 3 groups： sham operation group,model group,trimetazidine group [intragastric administration trimetazidine 5 mg/（ kg·d） ]for 6 weeks. At the end of the experiment,the left ventricular myocardium was removed and the malondialdehyde（ MDA） was determined by thiobarbital method. The superoxide dismutase（ SOD） was determined by xanthine oxidase method,and the pyruvate was determined by RT-PCR,then the pathomorphology and myocardial ultrastructure was observed. Results The activity of SOD was increased but the expression of MDA were decreased in the myocardium of tramadiazine group. The expression of pyruvate dehydrogenase（ PDH） mRNA was up-regulated after treated weith trimetazidine,which was higher than that in model group（ P 〈 0. 05）. The degree of myocardial injury in tramadamide group was lower than that in model group verified by light microscope and electron microscope detection（ P 〈 0. 05）. Conclusion Tramadiazine can improve oxidative stress in cardiomyocytes of heart failure dogs. The mechanism may be related to the reduction of nicotinamide adenine dinucleotide（ NADH） production,indirectly improving the expression of PDH mRNA,improving glucose oxidation,inhibiting lipid peroxidation,improving myocardial energy metabolism.

关 键 词：曲美他嗪 心力衰竭 丙二醛 超氧化物岐化酶 丙酮酸脱氢酶 

分 类 号：R541.62[医药卫生—心血管疾病]