缺氧应激下血管内皮细胞调控小胶质细胞表型及其机制

Mechanism of microglial phenotype regulated by vascular endothelial cells under hypoxia stress

目的研究缺氧应激下内皮细胞形态表型改变对小胶质细胞活化、趋化和吞噬活性的调控及机制,解释血-脑屏障(BBB)开放的双时相现象。方法采用鼠小胶质细胞系(BV2)和鼠血管瘤内皮细胞(EOMA)细胞株进行实验,制作内皮细胞缺氧损伤模型;将BV2细胞分别与正常及缺氧EOMA细胞共育培养,观察前者形态表型变化,检测其趋化和吞噬活性。结果BV2细胞与缺氧EOMA细胞共育培养后呈现抗炎表型,高表达趋化因子受体及吞噬活性表型。结论BV2细胞在趋化因子作用下同缺氧EOMA细胞直接接触,可能通过CD200-CD200R通路增强其抗炎和吞噬活性,短时间内有利于恢复血-脑屏障的正常功能。

Objective To observe morphological and phenotypic changes of endothelial cells under hypoxia stress.To investigate the mechanism of regulating microglia activity,chemotaxis and phagocytosis activity.Explaining the dual phase phenomenon of blood-brain barrier(BBB)opening.Methods The experiment was carried out with mouse microglia cell(BV2)and rat hemangioma endothelial cell(EOMA)cell line.Hypoxic damage model of endothelial cells was made.BV2 cells were co-cultured with normal and damaged EOMA cells so as to observe the morphological changes and their chemotaxis and phagocytic activity.Result BV2 cells showed anti-inflammatory phenotype,high expression of chemokine receptor and phagocytic active phenotype after co-cultured with hypoxia impaired EOMA cells.Conclusions BV2 cells enhance the anti-inflammatory and phagocytic activity probably through the CD200-CD200R pathway after direct contact with EOMA cells damaged by hypoxia.In short time it is beneficial to restore the normal function of the blood brain barrier.