蛋白酶体抑制剂MG-132对VMC小鼠氧化应激和凋亡的影响被引量：3

Effect of MG-132 on oxidative stress and apoptosis in mice with viral myocarditis

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摘要目的:研究泛素蛋白酶体抑制剂MG-132对病毒性心肌炎(viral myocarditis,VMC)小鼠氧化应激和凋亡的作用,探讨泛素蛋白酶体系统在病毒性心肌炎发病学中的作用机制。方法:随机将90只雄性BALB/C小鼠分为3组:正常对照组(n=30),心肌炎组(n=30),心肌炎+MG-132处理组(n=30)。腹腔接种柯萨奇B3病毒诱发急性心肌炎,MG-132处理组腹腔注射MG-132(0.75 mg/kg),连续给药7 d;对照组及心肌炎组腹腔注射DMSO溶剂。于第7天及第14天小鼠取材,观察心肌组织的病理改变,测定过氧化物丙二醛(MDA)、超氧化物歧化酶(SOD)水平,心肌凋亡变化以及各组存活率。结果:与正常对照组相比,心肌炎组小鼠MDA增高而SOD降低(P<0.01);心肌炎组的凋亡执行因子Caspase3水平及凋亡指数明显升高(P<0.01);同时小鼠死亡率显著增加。与心肌炎组相比,心肌炎+MG-132处理组第7天小鼠MDA水平有降低趋势但无统计学意义,SOD水平增加(P<0.05),第14天MDA水平降低(P<0.01),SOD水平增加(P<0.01);另外MG-132干预后Caspase3水平及凋亡指数明显下降(P<0.01),小鼠的死亡率减低,心脏病理损伤减轻明显(P<0.05)。结论:MG-132抑制泛素蛋白酶体系统可以减轻CVB3心肌炎小鼠氧化应激损伤及凋亡,具有心肌保护作用。泛素蛋白酶体系统参与了CVB3心肌炎的发病过程,泛素蛋白酶体抑制剂可能为急性病毒性心肌炎提供一种崭新的治疗方法。 AIM： To study the effect of ubiquitin proteasome inhibitor MG-132 on oxidative stress and apoptosis in mice with viral myocarditis and its mechanism. METHODS： 90 BALB / C mice were randomly divided into three groups（ 30 cased each）： the control group,CVB3 group and CVB3 ＋MG-132 group. CVB3 was inoculated intraperitoneally to induce myocarditis. CVB3 ＋ MG-132 group was injected with 0. 75 mg / kg MG-132 intraperitoneally for 7 d continuously. While the control group and CVB3 group were treated with same dose of DMSO. Pathological changes,levels of methane dicarboxylic aldehyde（ MDA） and superoxide dismutase（ SOD）,the myocardial apoptosis and survival rates of each group were detected. RESULTS： Compared with the control group,the level of MDA was increased and the level of SOD was decreased in CVB3 group（ P〈0. 01）. The expression levels of Caspase3 mRNA and protein were significantly increased,followed by the apoptosis index increased in CVB3 group（ P〈0. 01）. Meanwhile the mortality rate of CVB3 group was significantly increased.The level of MDA was decreased and the level of SOD was increased in CVB3 ＋ MG-132 group as compared with CVB3 group（ P〈0. 05）. And the expression levels of Caspase3 and the apoptosis index decreased as well as the mortality and pathological injury in CVB3 ＋ MG-132 group（ P〈0. 01,P〈0. 05）. CONCLUSION： MG-132 protects mice from CVB3-induced acute viral myocarditis through suppressing the oxidative stress and apoptosis,which indicates that ubiquitin proteasome-system maybe a potential new target therapy of viral myocarditis.

作者张新民李岳春陈鹏叶盛陈一和夏武杰

机构地区温州医科大学附属第二医院心内科

出处《中国临床药理学与治疗学》 CAS CSCD 2016年第9期984-988,共5页 Chinese Journal of Clinical Pharmacology and Therapeutics

基金温州市科技局科技计划项目(Y20130178) 国家自然科学基金项目(81570342)

关键词病毒性心肌炎 MG-132 氧化应激凋亡 VMC MG-132 oxidative stress apoptosis

分类号 R965.2 [医药卫生—药理学]

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