双层心外膜补片调控IntegrinαVβ3介导的巨噬细胞极化促进心肌修复的机制研究

心肌梗死后补片修补是促进心肌修复的有效手段，但机制未阐明。我们近期研究发现，双层心外膜补片可减小室壁应力，改善室壁顺应性；诱导巨噬细胞极化促进心肌修复（Huang.et al. Nature Medicine）。进一步预初试验发现，该补片可促进IntegrinαVβ3相关基因表达上调。但补片如何调控IntegrinαVβ3活性，是否介导巨噬细胞极化促进心肌修复尚不明确。本项目假设双层心外膜补片通过减少室壁应力，上调IntegrinαVβ3表达，促进巨噬细胞由促炎症型（M1型)向促修复型（M2型）极化，改善局部炎症微环境而促进心肌修复。为此，本项目研究：1、补片影响IntegrinαVβ3活性的机制；2、补片调控IntegrinαVβ3促巨噬细胞从M1向M2极化的机制；3、补片诱导极化的巨噬细胞促进心肌修复的机制。为阐明双层心外膜补片促梗死后心肌修复机制提供理论依据。

Epicardial implantation of cardiac patch after myocardial infarction (MI) can promote cardiac repair, but the specific mechanism is still unclear. Our recent research found that the bi-layered epicardial patch could reduce ventricular stress and improve the compliance of the ventricular wall; induce the macrophage polarization to promote cardiac repair (Huang.et al. Nature Medicine). Further research showed that the bi-layered epicardial patch could increase expression of IntegrinαVβ3-related genes. However, how the bi-layered epicardial patch regulates the IntegrinαVβ3 in macrophage to mediate macrophage polarization to promote cardiac repair is still unclear. Therefore, we propose that a bi-layered epicardial patch reduces ventricular stress, increases expression of IntegrinαVβ3-related genes, induces macrophage polarization from M1 to M2 and regulates local inflammatory microenvironment to improve cardiac repair. The study will be carried out: 1. How to regulate the IntegrinαVβ3 in macrophage by the bi-layered epicardial patch; 2. How the IntegrinαVβ3 affects macrophage polarization from M1 to M2 by the bi-layered epicardial patch; 3. The mechanism of polarized macrophages induced by the bi-layered epicardial patch promoting cardiac repair. The study aims to elucidate the mechanism of the bi-layered epicardial patch to cardiac repair after MI, and to provide a strong theoretical basis for the patch to treat MI.