病毒性心肌炎是临床较为常见的心血管疾病之一，其发病机制尚未完全清楚。我们前期研究发现，交感神经系统及肾上腺能相关受体在病毒性心肌炎中介导促炎作用，基于胆碱能抗炎通路在一些炎症与免疫性疾病中抗炎作用的发现，我们推测神经-免疫调节网络失衡参与了病毒性心肌炎的发生发展，其很可能成为心肌炎调控的一个新靶点。本项目以柯萨奇病毒B3嗜心肌株诱导的心肌炎小鼠为研究对象，从兴奋/阻滞α7烟碱型乙酰胆碱受体以及直接切断颈部迷走神经、激活/抑制胆碱能抗炎通路着手，利用分子生物学技术检测α7烟碱型乙酰胆碱受体、炎症细胞因子、NF-κB和JAK-STAT信号转导通路相关蛋白的水平，观察胆碱能抗炎通路在病毒性心肌炎中的作用，解析其抗心肌炎症的下游信号转导机制。本项目最大的特色是将心肌炎的机制研究深入神经免疫学领域，开展此项研究，不仅对心肌炎的发生发展机制提供新的认识，而且还可能对心肌炎的治疗提供一个崭新的思路。

Viral myocarditis is one of the most common cardiovascular diseases. However, the mechanisms involved in the pathogenesis of viral myocarditis are not well understood. Recently, we have found that excessive sympathetic activation in viral myocarditis aggravates in?ammatory lesions, and other studies have demonstrated that cholinergic antiinflammatory pathway exerts antiinflammatory effects through the α7 nicotinic acetylcholine receptor, and has been shown to be protective in several models of inflammatory diseases. Therefore, we hypothesized that dysfunctional neural-immune circuit might play an important role in the pathophysiology of viral myocarditis, and activation of cholinergic antiinflammatory pathway could offer a new therapeutic strategy for viral myocarditis. In the present study, we will investigate whether activation of cholinergic antiinflammatory pathway attenuates inflammation in a coxsackievirus B3 murine myocarditis model. The agonist and antagonist of α7 nicotinic acetylcholine receptor in different concentrations will be administered, and the right cervical vagus nerve will be cut off in the infected mice. The levels of α7 nicotinic acetylcholine receptor, inflammatory cytokines, NF-κB, pJAK and pSTAT protein expression within the myocardium will be determined using quantitative PCR. The most novel insight of the study is that the nervous system may modulate the inflammatory response in viral myocaditis. The study will help elucidate the novel mechanism involved in the pathogenesis of viral myocarditis, and open new possibilities in the therapeutic management of viral myocarditis.