Nox4介导线粒体自噬对柯萨奇B3病毒性心肌炎的作用机制

柯萨奇B3组病毒（CVB3）引起的病毒性心肌炎是一种严重影响人类健康的心血管疾病，其发病机制尚未阐明。活性氧（ROS）是参与心肌细胞损伤的重要因素之一，而Nox4是产生ROS 的重要来源。大量研究证实Nox4介导ROS生成参与调节多种心血管疾病，但对Nox4是否参与CVB3诱导心肌炎发病机制尚未见报道。本课题组前期研究显示CVB3诱导心肌损伤的同时，心肌组织中Nox4表达明显升高，且CVB3可诱导线粒体自噬，因此推测“柯萨奇B组病毒通过诱导心肌细胞Nox4活化，产生大量ROS，引起线粒体自噬及心肌细胞损伤”。为证实该假说，本课题拟采用CVB3诱导心肌细胞损伤的小鼠及细胞模型，利用激光共聚焦、免疫荧光、western blot等方法，观察心肌细胞Nox4表达、ROS释放与线粒体自噬的关系，阐明Nox4介导线粒体自噬对心肌细胞的损伤作用，为柯萨奇B组病毒诱导病毒性心肌炎阐述新机制。

Coxsackievirus B3-induced myocarditis is a cardiovascular disease that has a serious impact on the health of adolescents. The pathogenesis of the disease has not been elucidated. It has been researched that reactive oxygen species (ROS) is one of the important factors involved in the myocardial injury, and Nox4 is an important source of the generation of ROS.Studies have shown that Nox4-mediated ROS generation involved in the regulation of a variety of cardiovascular diseases, but it has not been reported whether or not Nox4 participate in the pathogenesis of viral myocarditis. Preliminary studies have showed that myocardial tissue has a significantly higher Nox4 expression, while it was being injured by CVB3. And CVB3 can induce the mitophagy of the myocardium, so we suggest that “Coxsackievirus B induced Nox4 activation of cardiomyocyte , produce large amounts of ROS, and cause mitophagy and damages of myocardium”. To confirm this hypothesis, observed the Nox4 expression and the relevance of ROS release and mitophagy , clarify the damage of myocardium caused by Nox4-mediated mitophagy , and to elaborated a new mechanism for the Coxsackievirus B-induced myocarditis. We will establish a model about mouse with Coxsackievirus B3-induced myocarditis, and use the method of confocal, immunofluorescence and western blot.