移植物血管病是影响心脏移植术后患者远期生存最关键因素，尚无有效治疗方案。其过程是持续慢性炎症损伤、血管病理重构。免疫及非免疫因素参与的慢性炎症微环境是其发生发展的基础，前期研究证实负向调控炎症微环境可有效缓解血管重构。巨噬细胞连接固有和获得性免疫，是炎症反应核心并具有强大负向调节能力。MFG-E8广泛分布于细胞外基质，是胞葬作用最重要桥接分子，可诱导巨噬细胞负向调控作用，并直接作用于内皮细胞、树突状细胞等发挥抗炎作用，与自身免疫病、肿瘤免疫逃逸密切相关。我们前期研究发现MFG-E8在移植物血管病患者及心脏移植小鼠中表达明显降低并体外诱导巨噬细胞向M2分化，但其作用及机制尚不明确。本课题将利用心脏移植模型，通过基因敲除、过继回输、凋亡细胞输注等方案联合体外实验，探讨MFG-E8介导的巨噬细胞负向调控对移植物炎症微环境的作用及机制，明确其对移植物血管重构的影响，为移植物血管病的治疗提供新思路。

Cardiac Allograft Vasculopathy（CAV）is the most important factor affecting the long-term survival of patients after heart transplantation. So far, there are no effective treatments for it. CAV is a pathological process caused by chronic inflammatory injury, excessive repair and vascular remodeling. The chronic inflammatory microenvironment consisting of immune and non-immune factors plays a key role in the progression of CAV. Previous studies have indicated that inhibiting the progress of inflammatory microenvironment can effectively alleviate allograft vascular remodeling. Macrophages connect innate immunity and adaptive immunity, serve as the core of mediating inflammation response, and have strong ability of negative regulation. MFG-E8, as a most important bridging molecule in efferocytosis, is widely distributed in the extracellular matrix. It can alleviate inflammatory response by promoting the differentiation of anti-inflammatory macrophages and directly acting on endothelial cells, dendritic cells and T cells. MFG-E8 is closely related to autoimmune diseases, atherosclerosis and tumor immune escape. Our previous studies demonstrated that the expression level of MFG-E8 was significantly decreased in patients with CAV and murine undergone heterotopic heart transplantation, but the role and mechanism remained unknown. To clarify these issues, we will establish murine heterotopic heart transplantation model and use gene knock out mice, adoptive cell transfer, apoptotic cell infusion and conduct vitro experiments. Ultimately this study may provide a novel therapeutic strategy for CAV.