IL-37负向调控心肌梗死后心室重塑的机制研究

心室重塑是心肌梗死（MI）后慢性心功能不全的主要病理生理机制。研究表明, 炎症免疫反应过度的激活加剧心室重塑。IL-37是新近发现的抗炎因子，在固有性和获得性免疫调节中起着重要保护作用。我们前期研究显示，外源性IL-37通过抑制炎症和氧化应激显著减轻小鼠缺血再灌注损伤。预实验表明，IL-37干预MI小鼠4周后，明显改善左室EF值及降低心室过度扩张，但其作用机制尚不清楚。我们推测，干预IL-37可调控炎症免疫反应及MI后心室重塑进程。为证实本假说，拟：1，利用IL-37tg小鼠构建MI模型，观察不同时间点小鼠心功能及心室重塑的变化；2，通过增强和阻断IL-37效应，探讨对体内TLR-4/NF-κB通路和巨噬细胞M1/M2极化、DC耐受状态、Tregs介导免疫炎症反应及MI后心室重塑的影响。本研究不仅阐明IL37在MI后心室重塑进程中的作用，并有望进一步完善IL-37介导的免疫炎症学机制。

Ventricular remodeling is a major Pathophysiological mechanism of cardiac dysfunction post myocardial infarction(MI). more and more evidences indicate that inflammatory immune response play a significant role in the development of ventricular remodeling. IL-37 is a newest Anti-inflammatory cytokine which play a important protective role in the innate and acquired immunity. our Preliminary study shows that exogenous IL-37 significantly ameliorates myocardial ischemia/reperfusion injury in mice by inhibiting inlammatory and Oxidative Stress. Pre-experiment indicates IL-37 can ameliorate LVEF and LVEDD of MI mices after 4 weeks. but it remains unclear with regard to its mechanism. We speculate that IL-37 can regulate inflammatory immune response and Ventricular remodeling post MI.To confirme the hypotheses: first, with IL-37tg mice MI modle, we observe cardiac function and ventricular remodeling at different timepoint.second,we explore the influence of IL-37 on TLR-4/NF-κB Signaling pathway ，M1/M2 balance,DC tolerance,Tregs-mediated inflammatory immune response and Ventricular remodeling post MI. In this study, we may clarify the role of IL-37 in Ventricular remodeling the process post MI,and further improve IL-37 mediated immunological mechanism.