摘要
目的:观察蛋白酶体抑制剂MG-132对病毒性心肌炎小鼠心肌细胞凋亡因子的作用,进一步探讨泛素蛋白酶体系统在病毒性心肌炎凋亡过程中的具体机制。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(CVB3)诱发急性心肌炎,次日处理组分别腹腔注射蛋白酶体抑制剂MG-132,连续给药7 d;对照组及心肌炎组腹腔注射DMSO溶剂。第14天观察小鼠存活率、心功能指标、心肌病理及心肌细胞凋亡因子变化。结果:与心肌炎组相比,MG-132组核因子-κB水平显著降低(P<0.05),促凋亡因子Bax水平明显降低(P<0.05),抑制凋亡因子Bcl-2水平明显上调(P<0.05),Bcl-2/Bax比值显著增加(P<0.05)。与心肌炎组相比,MG-132处理组显著减少心肌炎小鼠心肌细胞凋亡、改善血流动力学状况及生存率。结论:蛋白酶体抑制剂MG-132通过下调核因子-κB和Bax、上调Bcl-2水平,抑制急性病毒性心肌炎小鼠心肌细胞凋亡,改善心功能及生存率,具有心肌保护作用。
AIM： To observe the effects of proteasome inhibitor MG-132 on myocardial cell apoptosis factor in mice with viral myocarditis,and further to explore the specific mechanisms of the ubiquitin proteasome system in the process of apoptosis in viral myocarditis. METHODS： Ninety male BALB/C mice were randomly divided into 3 groups： the normal control group（ n = 30）,the myocarditis group（ n = 30）,and the myocarditis ＋ MG-132 treatment group（ n = 30）. Intraperitoneal inoculation of coxsackievirus B3 virus（ CVB3） was used to induce acute myocarditis. The treatment group was injected with proteasome inhibitor MG-132 intraperitoneally for a consecutive 7 d. The control group and myocarditis group were intraperitoneally injected with DMSO solvent. The survival rate of mice,cardiac function index,pathology and the changes of cardiomyocyte apoptosis factors were observed on the 8 th day.RESULTS： Compared with myocarditis group,the nuclear factor kappa B level in MG-132 treated group was significantly decreased（ P〈0. 05）,the level of Bax was significantly decreased（ P〈0. 05）,the level of Bcl-2 was significantly increased（ P〈0. 05）,and the Bcl-2/Bax ratio increased significantly（ P〈0. 05）. Compared with the myocarditis group,the MG-132 treatment group significantly reduced the cardiomyocyte apoptosis, the improvement of the hemodynamic status and the survival rate in the myocarditis mice. CONCLUSION：Proteasome inhibitor MG-132 can inhibit the apoptosis of cardiomyocytes and improve the cardiac function and survival rate in mice with acute viral myocarditis by down-regulating nuclear factor kappa B and Bax and up-regulating Bcl-2 level.
作者
张新民
陈鹏
叶盛
夏武杰
李岳春
ZHANG Xinmin;CHEN Peng;YE Sheng;XIA Wujie;LI Yuechun(Department of Cardiology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, Chin)
出处
《中国临床药理学与治疗学》
CAS
CSCD
2018年第5期498-503,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家自然科学基金项目(81570342)
温州市科技局科技计划项目(Y20170264)
