负荷2D-STE评估CG双通路调控细胞凋亡及M2巨噬细胞极化的心肌保护效应及其机制研究

目前，临床治疗AMI的组织缺血再灌注方法会引起心肌I/R损伤。前期工作表明，CG诱导IL-10调控双信号通路减轻心肌I/R损伤。研究发现，TGR5对心肌细胞有保护作用，可调控IL-10激活JAK1/STAT3通路并促进M2型巨噬细胞极化，均与心肌I/R损伤密切相关。负荷2D-STE可用于评价整体和局部的左心室功能。综上，提出假说：CG上调TGR5促进IL-10调控双通路诱导M2巨噬细胞极化改善心脏功能。本项目将利用CAI法构建心肌I/R损伤模型，通过负荷2D-STE技术评价大鼠整体和局部心肌功能，结合体外实验，进行细胞凋亡状态、机体炎症水平等指标检测，评价CG双通路调控细胞凋亡及M2巨噬细胞极化在大鼠心肌I/R损伤中的作用。在此基础上，探讨CG对心肌I/R损伤的作用和可能机制。本研究的顺利开展将有利于进一步阐明心肌I/R损伤的病理机制，并为临床应用CG缓解心肌I/R损伤提供理论和实验依据。

Recently tissue ischemia-reperfusion methods for clinical treatment of AMI cause myocardial I/R injury. Previous work has shown that CG-induced IL-10 regulates dual signaling pathways to reduce myocardial I/R injury. Studies have found that TGR5 has protective effects on myocardial cells, it can regulate IL-10 activation of JAK1/STAT3 pathway and promote polarization of M2 macrophages, which are closely related to myocardial I/R injury. 2D-STE can be used to evaluate global and local left ventricular function. In summary, a hypothesis is proposed: CG upregulates TGR5 promotes IL-10 regulation of dual pathways to induce polarization of M2 macrophages and improve cardiac function. This project will use the CAI method to construct a model of myocardial I/R injury, evaluate the overall and local myocardial function of the rat through the load 2D-STE technology, and combine in vitro experiments to detect indicators such as apoptosis status and body inflammation level, and evaluate the dual CG pathway regulation of apoptosis and M2 macrophage polarization in rat myocardial I/R injury. On this basis, the effects and possible mechanisms of CG on myocardial I/R injury were explored. The successful development of this study will help further clarify the pathological mechanism of myocardial I/R injury and provide theoretical and experimental basis for clinical application of CG to alleviate myocardial I/R injury.