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18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-132,0.75 mg/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组心肌炎症性浸润和变性坏死较CVB组显著减轻；心脏重量/身体重量比值CVB组为6.18±0.40、CVB+T组为5.32±0.38,差异有统计学意义(P<0.05).cTnI、BNP水平CVB组为(3.88±0.08)μg/L、(3002±256)pg/ml, CVB+T组为(1.52±0.05)μg/L、(1506±142)pg/ml,CVB+T组均降低(均P<0.05)；荧光定量PCR显示CVB3 mRNA水平CVB组(1.42±0.06)高于CVB+T组(0.72±0.04)(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 investigate the effect of ubiquitin-proteasome system on acute viral myocarditis induced by coxsackievirus B3 (CVB3) in mice. Methods BALB/C mice were intraperitoneal y 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. Nor-mal 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 cTnⅠand 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 cTnⅠand BNP were 1.52±0.05μg/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.
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