蛋白酶体抑制剂MG-132对柯萨奇B3病毒性心肌炎小鼠的作用研究

目的：研究泛素蛋白酶体抑制剂MG-132对柯萨奇B3（CVB3）病毒性心肌炎小鼠的作用，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80只雄性BALB／C小鼠分为4组（，2—20）：正常对照组、心肌炎组、心肌炎＋处理组、正常＋处理组。腹腔接种CVB3诱发急性心肌炎，次日腹腔注射MG-132，0．75mg／kg；连续给药7d，对照组腹腔注射PBS。第8天小鼠取材，观察心脏病理变化，测定心肌CVB3病毒复制及血清肌钙蛋白、脑钠肽水平。结果：MG-132显著减轻心肌炎小鼠心脏病理损伤，显著降低心脏重量／身体重量比值，MG-132干预后第8天小鼠血清肌钙蛋白、脑钠肽水平显著降低，同时荧光定量PCR显示CVB3mR—NA复制水平显著降低。结论：MG-132通过抑制CVB3病毒复制，显著减轻心肌炎小鼠心脏病理损伤，起到保护心肌作用。

Effect of MG-132 in mice with acute viral myocarditis

AIM： To determine the ettect ot proteasome inhibitor MG-132 in mice with acute viral myocarditis induced by eoxsackievirus B3 virus （CVB3） infection. METHODS： BALB/C mice were intraperitoneally inoculated with CVB3 to induce myocarditis. From 24 h after in fection, MG-132 was administered at a dose of 0.75 mg/kg for 7 d continuously by intraperito- neal injection. Normal controls were treated with same volume of PBS. Then, the myocardial histopathological changes, HW/BW ratio, ex pression of myocardial CVB3 mRNA and serum cTn I and BNP were determined. RESULTS： MG-132 significantly attenuated myocardial le-sions and decreased HW/BW ratio. It also re markably decreased serum cTn I and BNP, down-regulated CVB3 mRNA expression com- pared with myocarditis controls. CONCLU SION： MG-132 protects against CVB3 induced viralmyocarditis in mice. MG-132 exerts its ben- eficial effect by downregulating CVB3 mRNA expression probably.