泛素蛋白酶体系统对CVB3病毒性心肌炎小鼠的作用研究  

Effect of ubiquitin-proteasome system on acute viral myocarditis in mice

作　　者：张新民[1] 陈鹏[1] 张素勤[1] 吴连拼[1] 李岳春[1] 

机构地区：[1]温州医学院附属第二医院心内科,325027

出　　处：《浙江医学》2013年第5期338-340,I0001,共4页Zhejiang Medical Journal

基　　金：国家自然科学基金资助项目（81200165）

摘　　要：目的通过抑制CVB3病毒性心肌炎小鼠中泛素蛋白酶体途径，研究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72只雄性BALB／c小鼠随机分为心肌炎组（CVB组）、心肌炎＋泛素蛋白酶体抑制剂MG-132处理组（CVB＋T组）、正常对照组（Sham组）、正常对照＋处理组（Sham＋T组），每组各侣只。前两组腹腔接种CVB3病毒诱发急性心肌炎，后两组腹腔注射PBS，CVB＋T组和Sham＋T组次日腹腔注射MG-132，0．75mg／kg，连续给药7d。第8天取材，观察小鼠心肌组织病理变化，测定心肌CVB3病毒复制及血清肌钙蛋白I（cTnI）、脑钠肽（BNP）水平。结果心肌病理检查显示．Sham组与Sham＋T组未见异常变化，CVB＋T组心肌炎症性漫润和变性坏死较CVB组显著减轻；心脏重量／身体重量比值CVB组为618：4-O40、CVB＋T组为5．32±038，差异有统计学意义（P〈0．05）。cTnl、BNP水平CVB组为（3．88±0．08）ug／L、（3002±256）pg／ml，CVB＋T组为（1．52±005）ug／L、（1506±142）pg／ml，CVB＋T组均降低（均P〈0．05）；荧光定量PCR显示CVB3mRNA水平CVB组（142±006）高于CVB＋T组（0．72±004）（P〈0．05）。结论抑制泛素蛋白酶体途径减少了CVB3病毒复制，显著减轻心肌炎小鼠心脏病理损伤，起到保护心肌的作用。Objective To i coxsackievirus B3 （CVB3） in mice nvestigate the effect of ubiquitin-proteasome system on acute viral myocarditis induced by Methods BALB/C mice were intraperitoneally inoculated with CVB3 to induce myocarditis From 24 h after infection, MG-132 was administered at a dose of 0.75 mg/kg for 7d continuously by intraperitoneal injection. Normal controls were treated with same volume of PBS. Then, the myocardial histopathological changes, heart weight/body weight ratio （HW/BW）, expression of myocardial CVB3 mRNA and serum cTn I and BNP levels were determined. Results Proteasome inhibitor MG-132 significantly attenuated myocardial lesions. HW/BW ratio was 6.18±0.40 in CVB group and 5.32±0.38 in MG-132 treatment group （CVB＋T）, respectively （P〈0.05）. The levels of serum cTn I and BNP were 1.52 ± 0.05 IJ g/L and 1 506 ± 142pg/ml in CVB＋T group, which were significantly lower than those in control group （P〈0.05）. MG-132 also remarkably down-regulated CVB3 mRNA expression compared with CVB group （0.72 ± 0.04 vs 1.42 ± 0.06, P〈0.05）. Conclusion MG-132 protects mice from viral myocarditis induced by CVB3, which is associated with down-regulation of CVB3 mRNA expression.

关 键 词：泛素蛋白酶体系统 小鼠 心肌炎 

分 类 号：R741[医药卫生—神经病学与精神病学]