血管内皮细胞损伤后的功能障碍在脑血管病发生发展中具有重要作用，内皮祖细胞（EPCs）的迁移、着床等功能状态直接决定内皮损伤的修复能力。揭示影响EPCs功能的调控因素及其分子机制有重要的理论和现实意义。环境因素可诱发脑血管疾病，然而其机制尚不清楚。申请者前期研究发现环境污染物二恶英活化其受体AhR可抑制EPCs的趋化迁移能力，提示AhR可调控EPCs功能。趋化因子SDF-1α及表达在EPCs表面的CXCR4对EPCs维持修复功能非常重要。我们还发现CXCR4启动子区存在AhR结合位点，AhR是否在CXCR4表达及EPCs功能调控中具有重要作用，目前尚未见报道。本项目拟通过大鼠颈动脉内皮损伤模型和染色质免疫共沉淀等技术，从动物、细胞、分子等多层面阐明环境因素通过AhR抑制SDF-1α/CXCR4轴调控EPC功能，进而影响血管内皮修复进程，从而为脑血管疾病的防治提供新靶点。

ndothelial injury and dysfunction play crucial roles in the occurrence and development of cerebrovascular disease(CVD).The ability of migration and homing represent Endothelial progenitor cells' (EPCs)repairing capacity for endothelial injury.It is of important theoretic and realitic significance to illuminate the regulatory factors and mechanism of EPCs' functions. The environment pollutants attribute much to CVD, although the mechanism is still unclear. We have showed that the typical environment pollutant, TCDD, an aryl hydrocarbon receptor (AhR) agonist, significantly inhibited the chemotaxis and migration of EPCs,which suggested that AhR modulate EPCs’ functions. The chemotactic factors, stromal cell derived factor-1α (SDF-1α) and it’s recepter,CXCR4,which exits on the EPCs,are pivital for EPCs to keep its endothelial repairing function. We found that an AhR binding site exists in CXCR4 promoter, no research was reported whether AhR plays an important role in CXCR4 expression and regulation of EPCs function. In this proposal, we plan to use the animal model of the carotid artery endothelial injury,chromatin immunoprecipitation (ChIP) technique, and so on , from the animal, cell, molecule levels, to elucidate that the environment factors inhibit SDF-1 α /CXCR4 axis and regulate EPCs’ function through the AhR, thereby affecting vascular endothelial repair process, to provide new ideas for prevention of cerebrovascular diseases.