巨噬细胞在脑血管损伤修复过程中的作用及机制

To focus on the research area "roles and mechanisms of macrophages in the repair of blood vessel injuries" in the annual guide, this project includes four labs in the fields of macrophage, cerebrovascular repair and regeneration, and lymphatic vessels. Mainly based on our previous publication reporting that macrophages mediate the repair of brain vascular rupture through direct physical adhesion and mechanical traction (Liu et al., Immunity 2016), this project will proceed in-depth studies of roles and mechanisms of macrophages in the brain vascular repair and regeneration. Four specific aims are included in this project. 1) Cell behavior studies of macrophages in response to brain vascular injury and other cell type injuries. 2) Identification and characterization of key molecules involved in the macrophage-mediated cerebrovascular repair. 3) Roles and mechanisms of macrophages in the homeostasis and repair of brain blood barrier. 4) Roles and mechanisms of macrophages in the meningeal lymphatics-mediated regional cerebrovascular regeneration.

针对本年度指南中集成项目的第一个资助方向“巨噬细胞在血管损伤、修复过程中的作用及机制”，以本计划资助项目已取得的重要成果“巨噬细胞通过直接粘附血管断点和产生机械收缩力修复断裂脑微血管（Liu et al., Immunity 2016）”为主要基础，本集成项目组集中了四位从事巨噬细胞、脑血管和淋巴管研究的本重大研究计划的项目负责人，组建了优势互补的研究团队，以斑马鱼和小鼠为主要模式动物，致力于从以下四个部分深入研究巨噬细胞在脑血管再生修复过程中的功能和作用机制：1）巨噬细胞响应脑血管断裂和其它脑组织损伤的细胞行为差异研究；2）巨噬细胞修复断裂脑血管关键调控因子的筛选鉴定及其功能机制研究；3）巨噬细胞在血脑屏障稳态维持及损伤修复中的功能及作用机制；4）巨噬细胞在脑膜淋巴管介导的脑血管再生中的功能及作用机制。

本项目顺利完成任务书中各项研究计划，主要包括：1）发现A1类清道夫受体（SR-A1）促进组织修复性巨噬细胞增殖，拮抗扩张性心肌病；2）发现巨噬细胞SR-A1-VEGF-B反应轴对肥胖性高血压的调节作用；3）发现MVP抑制IKK-NFkB通路介导的巨噬细胞炎症反应以减轻动脉粥样硬化病变进展；4）揭示巨噬细胞通过感应ATP发挥直接修复断裂脑微血管的功能；5）发展了器官再生过程中同时检测多个基因表达的高灵敏高分辨检测方法。