LILRB4招募SHP-1在心肌缺血再灌注损伤中的作用及机制研究

心肌缺血再灌注损伤（MIRI）是降低冠心病患者再灌注治疗效果的重要因素，其发病机制与炎症、氧化应激及凋亡密切相关。课题组前期研究提示，MIRI可促进白细胞免疫球蛋白样受体B4(LILRB4)应激性表达，而上调LILRB4可抑制缺氧复氧（H/R）诱导的心肌细胞凋亡、氧化应激及炎症反应。同时，LILRB4与蛋白酪氨酸磷酸酶-1(SHP-1)之间可能存在靶向调控作用。据此合理推测，LILRB4可通过募集SHP-1来抑制炎症、氧化应激及凋亡等病理生理过程，对MIRI的心肌发挥多重保护作用。为验证此假设，本项目拟以原代心肌细胞和心肌细胞LILRB4特异性敲除、过表达小鼠为研究对象，探讨LILRB4通过招募SHP-1来调节TLR4、ASK1、MyD88等相关信号通路的作用机制，评价LILRB4对MIRI诱导的炎症、氧化应激及凋亡反应的影响，为确立LILRB4作为MIRI防治新靶点提供理论依据。

Myocardial ischemia reperfusion injury (MIRI) is one of the most important factors which could reduce the effect of reperfusion therapy in patients with coronary artery disease. Its pathogenesis is closely related to the activities of inflammation, oxidative stress and apoptotic cascades. On the basis of our previous studies, MIRI enhanced the expression of stress-induced leucocyte immunoglobulin-like receptor subfamily B4 (LILRB4), while up-regulated LILRB4 attenuated cardiomyocyte apoptosis, oxidative stress and inflammation induced by hypoxia-reoxygenation (H/R). Additionally, there may be targeted regulatory relations between LILRB4 and SHP-1. Therefore, this study attempts to make a reasonable speculation that LILRB4 may suppress the inflammation, oxidative stress and cardiomyocyte apoptosis induced by MIRI through recruiting SHP-1, exerting multiple protective functions against MIRI. Based on this, we will take neonatal rat myocardial cells, LILRB4-CKO mice and LILRB4-CTG mice as the research object to analyse the mechanism of LILRB4 regulating TLR4, ASK1, MyD88 and other related signaling pathways by recruiting SHP-1, evaluating the multiple protective effects of LILRB4 on MIRI, in order to provide theoretical and experimental evidence for gene therapy in MIRI.