摘要
目的观察神经元-小胶质细胞间EphA4/ephrin信号通路在脑缺血后的炎性损伤中的作用及机制。方法建立神经元-小胶质细胞混合培养体系和糖氧剥夺再复氧(oxygen-glucose deprivation and reperfusion, OGD/R)模型,使用预聚集化的EphA4-Fc激动小胶质细胞ephrin配体,检测OGD/R后的细胞凋亡、小胶质细胞增殖和亚型极化以及小胶质细胞功能改变。结果 EphA4受体高表达于原代神经元,与对照组相比,预聚集化EphA4-Fc干预加重OGD/R导致的细胞凋亡,促进小胶质细胞增殖以及向M1型(促炎型)极化(炎症表型)。结论神经元-小胶质细胞间EphA4/ephrin信号通路通过调控小胶质细胞亚型极化参与脑缺血后的炎性损伤的过程。
Objective To investigate the role of neuron-microglia communication via EphA4/ephrin signaling pathway in inflammatory injury after ischemia and its mechanism. Methods Neuron-microglia co-culture system was constructed, as well as the oxygen-glucose deprivation and reperfusion(OGD/R) model was established. Pre-clustered EphA4-Fc was used as the agonist of microglial ephrin ligand. Then EphA4/ephrin signaling between neuron and microglia, namely OGD/R induced apotosis, microglial proliferation, polarization and function changes were analyzed. Results EphA4 receptor was highly expressed in primary neurons.Comparing to control group, pre-clustered EphA4-Fc intervention aggravated OGD/R-induced apoptosis as well as promoted microglial proliferation and its polarization to M1 type(inflammatory phenotype). Conclusion EphA4/ephrin signaling pathway between neuron and microglia was involved in the post-ischemic inflammatory injury by regulating polarization of microglia subtype.
引文
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