CAJ | 학술논문

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.
목적통과억제CVB3병독성심기염소서중범소단백매체도경,연구범소단백매체계통재병독성심기염발병중적작용궤제.방법장72지웅성BALB/c소서수궤분위심기염조(CVB조)、심기염+범소단백매체억제제MG-132처리조(CVB+T조)、정상대조조(Sham조)、정상대조+처리조(Sham+T조),매조각18지.전량조복강접충CVB3병독유발급성심기염,후량조복강주사PBS,CVB+T조화Sham+T조차일복강주사MG-132,0.75 mg/kg,련속급약7d.제8천취재,관찰소서심기조직병리변화,측정심기CVB3병독복제급혈청기개단백I(cTnI)、뇌납태(BNP)수평.결과심기병리검사현시,Sham조여Sham+T조미견이상변화,CVB+T조심기염증성침윤화변성배사교CVB조현저감경;심장중량/신체중량비치CVB조위6.18±0.40、CVB+T조위5.32±0.38,차이유통계학의의(P<0.05).cTnI、BNP수평CVB조위(3.88±0.08)μg/L、(3002±256)pg/ml, CVB+T조위(1.52±0.05)μg/L、(1506±142)pg/ml,CVB+T조균강저(균P<0.05);형광정량PCR현시CVB3 mRNA수평CVB조(1.42±0.06)고우CVB+T조(0.72±0.04)(P<0.05).결론억제범소단백매체도경감소료CVB3병독복제,현저감경심기염소서심장병리손상,기도보호심기적작용.
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.