蛋白酶体抑制剂减少病毒性心肌炎小鼠炎症因子IL-6和TNF-α的表达  

Proteasome inhibitors decrease IL-6 and TNF-α levels in mouse acute viral myocarditis

作　　者：张新民[1] 陈鹏[1] 叶盛[1] 夏武杰 李岳春[1] 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)

机构地区：[1]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》2017年第4期406-411,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(Y20130178)

摘　　要：目的:研究泛素蛋白酶体抑制剂对病毒性心肌炎小鼠炎症反应的作用,探讨泛素蛋白酶体系统在病毒性心肌炎发病中的作用机制。方法:将100只雄性BALB/C小鼠随机分为正常对照组,心肌炎组,心肌炎+bortezomib处理组与心肌炎+MG-132处理组,每组各25只。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bortezomib或者MG-132,连续给药7 d;对照组腹腔注射空白溶剂。第8天小鼠取材,观察心肌组织的炎症病理改变,电镜观察心肌细胞的超微结构改变,ELISA法检测心肌组织炎症因子IL-6、TNF-α的蛋白表达水平,嗜中性多型核白细胞(polymorphonuclear neutrophils,PMN)计数以及各组存活率。结果:与正常对照组相比,心肌炎组的IL-6、TNF-α水平,PMN计数均显著增加(P<0.05)。电镜下观察可见心肌炎组弥漫性心肌细胞肿胀、大量肌丝溶解线粒体肿胀空化。与心肌炎组相比,心肌炎+bortezomib处理组及MG-132处理组炎症因子的表达及PMN的浸润显著减少,心肌细胞损伤程度明显减轻,生存率显著提高(P<0.05)。结论:泛素蛋白酶体抑制剂通过降低CVB3心肌炎小鼠心肌组织中炎症因子的表达,减轻心肌损伤,提高生存率。泛素蛋白酶体系统参与了CVB3心肌炎的发病过程,此酶体系统可能是急性病毒性心肌炎治疗的潜在靶点。AIM： To investigate the effect of proteasome inhibitor in mice with inflammatory reaction of acute viral myocarditis induced by coxsack- ievirus B3 virus （ CVB3 ） infection. METHODS ： 100 male BALB/C mice were randomly divided into four groups, i.e. the normal control group, CVB3 group, CVB3 and bortezomib group, CVB3 and MG- 132 group. Mice in control group were injected with blank solvent, while mice in other three groups were intraperitoneally inoculated with CVB3 to induce a- cute viral myocarditis. 24 h after infection, mice in treatment groups were administrated with bortezomib or MG-132 respectively for 7d continuously by intra- peritoneal injection. Changes of myocardial ultra- structure, the mRNA and protein levels of IL-6 and TNF-α, the number of PMN, and the Survival rate of each group were detected. RESULTS： Compared with control group, the protein levels of IL-6 and TNF-α, and the number of polymorphonuclear neutrophils （PMN） were significantly increased in CVB3 group （P 〈 0.05 ）. The cardiomyocytes were diffused and swelled, the myofilament was lysed, and the mitochondria was swelled and vacuolizated. The above mentioned inflammatory factors in borte- zomib group and MG-132 group were significantly decreased as compared with CVB3 group （P 〈 0.05）. The damaged degree of the cardiomyocytes in treatment groups were less, and the mortality due to deadly arrhythmia were lower than that in CVB3 group. CONCLUSION： Proteasome inhibitors protect the mice from CVB3-induced acute viral myo-carditis by suppressing the expression of inflammatory factors. Ubiquitin proteasome system is a potential new target therapy for viral myocarditis.

关 键 词：病毒性心肌炎 MG-132 炎症因子 嗜中性多型核白细胞 IL-6 TNF-Α 

分 类 号：R965.2[医药卫生—药理学]