【摘要】 目的:观察RIP3/CaMKⅡ信号通路对柯萨奇病毒B3（CVB3）诱导的重症病毒性心肌炎小鼠心脏功能及生存曲线的影响,并探讨CaMKⅡ特异性抑制剂KN-93对心肌损伤的作用。方法:将60只雄性BALB/c小鼠分为正常对照组、CVB3组、CVB3+KN-93组和CVB3+KN-93+Ti（活性氧簇特异性抑制剂）组,以上小鼠腹腔及尾静脉注射药物连续7 d。采用双抗体夹心免疫法检测小鼠心肌细胞坏死标志物,心脏超声技术检测小鼠心脏结构和功能,绘制Kaplan-Meier生存曲线,观察KN-93对小鼠心肌的保护作用。结果:CVB3+KN-93组小鼠心肌细胞坏死较CVB3组显著减轻,心脏功能和生存曲线改善（P<0.01）;CVB3+KN-93组小鼠心肌组织H₂O₂含量较CVB3组显著下降（P<0.01）;加入Ti后,CVB3+KN-93+Ti组H₂O₂含量较CVB3+KN-93组轻度下降（P<0.05）,但无论是心脏功能还是生存曲线均无显著差异。结论:RIP3/CaMKⅡ信号通路在CVB3诱导的急性重症病毒性心肌炎小鼠心肌细胞损伤中起到主导作用;KN-93能阻断这种作用并可能产生新的治疗方式,其效果可能是通过对CaMKⅡ的直接抑制和对活性氧簇的间接抑制而实现的。更多还原

【Abstract】 AIM:To investigate the effects of RIP3/CaMKⅡ signaling pathway on Coxsaekie virus B3（CVB3）-induced severe viral myocarditis and to explore the role of CaMKⅡ specific inhibitor KN-93 in severe viral myocarditis.METHODS:Male BALB/c mice（n=60）were divided into normal control group,CVB3 group,CVB3+KN-93 group and CVB3+KN-93+Ti（reactive oxygen species specific inhibitor）group.The myocardial necrosis markers were detected by double-antibody sandwich immunoassay.The structure and function of mouse heart were detected by echocardiography,and Kaplan-Meier survival curve was drawn to observe the protective effect of KN-93 on the mice with myocardial injury.RESULTS:Compared with CVB3 group,significantly reduced myocardial cell necrosis,improved cardiac function and survival curve of the mice were observed in CVB3+KN-93 group（P<0.01）.The content of H₂O₂ in CVB3+KN-93 group was significantly lower than that in CVB3 group（P<0.01）.After adding Ti,H₂O₂ content in CVB3+KN-93+Ti group was slightly lower than that in CVB3+KN-93 group（P<0.05）,but the improvement of cardiac function and survival curve was not obvious.CONCLUSION:RIP3/CaMKⅡ signaling pathway plays a significant role in cardiomyocyte death induced by viral infection.KN-93 blocks this pathway and may serve as a new therapeutic option for the treatment of severe viral myocarditis.The mechanism may be related to the direct inhibition of CaMKⅡ and the indirect inhibition of reactive oxygen species.更多还原