曲美他嗪对病毒性心肌炎小鼠的保护作用及其机制  

Protective Effect and Mechanism of Trimetazidine on Viral Myocarditis in Mice Model

作　　者：孙艳侠[1] 王国干[1] 崔小岱[2] 高鑫[1] 孙春荣[2] 

机构地区：[1]北京协和医学院 中国医学科学院 阜外心血管病医院急重症中心,北京市100037 [2]首都儿科研究所中心实验室

出　　处：《中国循环杂志》2012年第3期224-227,共4页Chinese Circulation Journal

摘　　要：目的:观察曲美他嗪对M株柯萨奇病毒B3(CVB3m)感染的病毒性心肌炎小鼠的保护作用并探讨其可能作用机制。方法:以CVB3m诱导的病毒性心肌炎Balb/c小鼠模型为研究对象。201只清洁级近交系4～6周龄雄性Balb/c小鼠随机分成5组。正常对照小鼠20只(正常组);病毒性心肌炎小鼠55只(心肌炎组);喂养曲美他嗪10 mg/(kg.d)的正常小鼠20只(药物对照组);喂养曲美他嗪10 mg/(kg.d)的病毒性心肌炎小鼠53只(低剂量治疗组);喂养曲美他嗪20 mg/(kg.d)的病毒性心肌炎小鼠53只(高剂量治疗组)。观察各组血清中肌钙蛋白I(cTnI)水平、血清中超氧化物歧化酶(SOD)、丙二醛(MDA)含量的变化以及心肌组织中Fas mRNA表达水平的变化。结果:小鼠感染CVB3m后第7天及第14天,与正常组及药物对照组比较,心肌炎组、低剂量治疗组和高剂量治疗组血清cTnI水平、MDA含量显著升高,SOD含量显著降低,Fas mRNA的表达显著增加,差异有统计学意义(P<0.05)。小鼠感染CVB3m后第7天,与心肌炎组比较,低剂量治疗组和高剂量治疗组血清cTnI水平显著降低,MDA含量显著降低,差异有统计学意义(P<0.05),与心肌炎组及低剂量组比较,高剂量治疗组SOD含量显著升高,Fas mRNA的表达显著减少,差异有统计学意义(P<0.05)。感染CVB3m后第14天,与心肌炎组比较,低剂量治疗组和高剂量治疗组血清cTnI水平、MDA含量显著降低,SOD含量显著升高,Fas mRNA的表达显著减少,差异有统计学意义(P<0.05),与低剂量治疗组比较,高剂量治疗组上述指标变化更明显,差异有统计学意义(P<0.05)。结论:曲美他嗪能够减少病毒性心肌炎中心肌细胞的损害。其机制可能与其抗氧化作用以及通过下调Fas mRNA水平抑制心肌细胞凋亡有关。Objective：To observe the protective effect and mechanism of trimetazidine on viral myocarditis in mice model. Methods ：A total of 201 male mice were randomly divided into 5 groups. Normal control group, n = 20, Myocarditis group ,n = 55, the myocarditis was induced by Coxsackievirus B3 （ CVB3 ） ; Trimetazidine control group, n = 20, the normal mice were fed with trimetazidine 10 mg/（ kg ~ d）, Low dose group, n = 53, myocarditis mice were treated with trimetazidine 10 mg/（ kg ~ d） and High dose group, n = 53, myocarditis mice were treated with trimetazidine 20 mg/（ kg ~ d）. Effect of trimetazidine on serum levels of cardiac troponin I （cTnI） , super oxide dismutase （SOD） and maleic dialdehyde （MDA） were examined and Fas mRNA expression in myocardium was analyzed by real-time PCR. Results ： At 7 and 14 days after CVB3 infection, compared with Normal control and Trimetazidine control groups, the serum levels of cTnI, MDA and Fas mRNA expression increased, SOD decreased in Myocarditis, Low dose and High dose groups, P〈 0.05 respectively. At 7 days after infection, compared with Myocarditis group, cTnI and MDA decreased in Low dose and High dose groups,P〈0. 05 respectively. Compared with Myocarditis and Low dose groups, SOD increased, Fas mRNA decreased in High dose group, P〈0. 05 respectively. At 14 days after infection, compared with Myocarditis group, SOD increased, cTnI, MDA and Fas mRNA expression decreased in Low dose and High dose groups,P〈0. 05 respectively. Conclusion： Trimetazidine could decrease the myocardium injury in myocarditis mice model, this might be because of its antioxidant activity and the inhibition of Fas mRNA expression.

关 键 词：心肌炎 曲美他嗪 氧自由基 凋亡 FAS 

分 类 号：R972.4[医药卫生—药品]