RIP3/CaMKⅡ信号通路对重症病毒性心肌炎小鼠心脏功能及生存曲线的影响  

Effects of RIP3/CaMKⅡ signaling pathway on cardiac function and survival curve in mice with severe viral myocarditis

作　　者：周飞[1] 滕林[1] 邹文博[1] 杨俊[1] 丁家望[1] 李松[1] ZHOU Fei;TENG Lin;ZOU Wen-bo;YANG Jun;DING Jia-wang;LI Song(Department of Cardiology,Yichang Central People's Hospital,The First College of Clinical Medical Sciences,China Three Gorges University,Yichang 443003,China)

机构地区：[1]三峡大学第一临床医学院,宜昌市中心人民医院心内科,湖北宜昌443003

出　　处：《中国病理生理杂志》2021年第1期146-150,共5页Chinese Journal of Pathophysiology

基　　金：湖北省卫生厅青年人才基金项目(No.WJ2019Q016)。

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。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.

关 键 词：病毒性心肌炎 柯萨奇病毒B3 RIP3/CaMKⅡ信号通路 活性氧簇 

分 类 号：R542.21[医药卫生—心血管疾病] R363.2[医药卫生—内科学]