心肌缺血再灌注损伤是影响冠心病患者预后的重要因素，而炎症在再灌注损伤中起着重要作用。炎症因子白介素17（IL-17）是激活固有免疫和宿主防御的重要始动因子，再灌注损伤时T细胞来源的IL-17A通过募集中性粒细胞等放大炎症反应，导致心肌损伤。我们前期研究发现IL-17A结合心肌细胞表面IL-17RA/IL-17RC受体激活胞内Stat3信号通路和诱导iNOS表达，介导心肌细胞凋亡。但IL-17及其受体家族介导再灌注心肌损伤的确切机制尚未阐明。因此，本研究拟应用小鼠心肌缺血再灌注模型，观察IL-17A及其受体家族成员在心肌的表达和分布特征，阐明受体亚型在介导心肌收缩、氧化应激和内质网应激中的作用和机制；同时研究IL-17A直接作用下心肌细胞旁分泌IL-17F对诱导成纤维细胞表型转化和晚期心室重塑的分子机制，为寻找缺血再灌注心肌损伤的有效治疗靶点提供理论和实验依据。

Myocardial ischemia-reperfusion (IR) injury has great effects on prognosis of patients with coronary artery disease. Accumulating evidences have demonstrated that inflammation plays a pivotal role in myocardial injury during IR. Interleukin-17 (IL-17), an inflammation factor, initiates innate immunity and host defense. IL-17A, secreted by T cells, recruits neutrophils to the injured heart, exacerbating inflammation which may lead to myocardial injury. However, it remains unknown whether and how IL-17A act on cardiomyoytes. Our preliminary data suggest that IL-17A may act on cardiomyocytes to promote apoptosis through Stat3 signaling pathway. We aim to characterize the IL-17 and its receptors family employing myocardial IR model in mice and their roles in cardiac contractility, reactive oxygen stress (ROS) and endoplasmic reticulum stress. Furthermore, we propose the effects of IL-17F on switching fibroblast phenotype and late ventricular remodeling, which is paracrined by cardiomyocytes under stimulation of IL-17A. This proposal will provide insights into the molecular mechanisms of myocardial injury, thereby providing theoretical and experimental evidences for targeting therapy in myocardial injury during ischemia reperfusion.