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目的：通过建立大鼠海马神经元氧糖剥夺（OGD）模型，探讨 orexin-A（OXA）对缺氧状态海马神经元的作用及其潜在机制。方法Wistar 大鼠海马神经细胞分为对照组、氧糖剥夺组（OGD 组）、氧糖剥夺加 OXA 组（OGD ＋OXA 组，包括 OGD ＋OXA 1 nmol／L 组、OGD ＋OXA 3 nmol／L 组、OGD ＋OXA 10 nmol／L 组、OGD ＋OXA 100 nmol／L 组）、氧糖剥夺加 U0126组（OGD ＋U0126组）和氧糖剥夺加 OXA、U0126组（OGD ＋OXA ＋U0126组）。取原代海马神经元培养72 h 后，氧糖剥夺以建立缺氧损伤模型，后分别加入不同终浓度的 OXA（1、3、10、100 nmol／L），于48 h 观察 OXA 对海马神经元凋亡率的影响；并利用 U0126阻滞 ERK1／2通路，通过 Western blotting及细胞凋亡率检测，探究 OXA 对海马神经元凋亡率影响的分子机制。结果与 OGD 组相比，OGD ＋OXA 3 nmol／L组、OGD ＋OXA 10 nmol／L 组和 OGD ＋OXA 100 nmol／L 组的细胞凋亡率均显著增加（P ＜0．01）；OGD ＋OXA 10 nmol／L组和 OGD ＋OXA 100 nmol／L 组的细胞凋亡率高于 OGD ＋OXA 3 nmol／L 组（P ＜0．01），而二者之间无统计学差异（P ＞0．05）。U0126预处理后，OGD ＋U0126组海马神经元的凋亡率明显低于 OGD 组（P ＜0．01）；OGD ＋U0126＋OXA 组的海马神经元凋亡率明显低于 OGD ＋OXA 100 nmol／L 组（P ＜0．01）。结论高浓度 OXA 对海马神经元有损害作用，并加重缺氧状态下的神经元损害，其作用机制与 OXA 过度激活 ERK1／2信号通路有密切关系。“,”Objective To investigate the effects of orexin-A (OXA)on the hippocampal neurons of Wistar rats in the state of oxygen glucose deprivation (OGD)and its potential mechanism.Methods Hippocampal nerve cells of Wistar rats were divided into the control group,OGD group,OGD +OXA groups (including OGD +OXA 1 nmol/L group, OGD +OXA 3 nmol/L group,OGD +OXA 10 nmol/L group and OGD +OXA 100 nmol/L group),OGD +U0126 group,and OGD +OXA +U0126 group.The hypoxia models of primary hippocampal neurons were built after 72-hour culture,and then different concentrations of OXA (1,3,10 and 100 nmol/L)were added in after OGD.The effects of OXA on the apoptotic rate of hippocampus neurons were detected 48 hours later.MAPK/ERK1 /2 pathway was blocked by U0126 to investigate the molecular mechanism.Results Compared with OGD group,the apoptotic rates of hippocampal cells of OGD +OXA 3 nmol/L group,OGD +OXA 10 nmol/L group and OGD +OXA 100 nmol/L group were signifi-cantly increased (P 0.05),while the cell apoptotic rate of these two groups were higher than that of OGD +OXA 3 nmol/L group (P <0.01).After U0126 treatment,the apoptotic rate of hippocampal neurons of OGD +U0126 group was significantly lower than that of OGD group (P <0.01),and that of the OGD +U0126 +OXA group was lower than OGD +OXA 100 nmol/L group (P <0.01).Conclusion OXA at high concentration can aggravate the damage ofOGD on hippocampal neurons,which closely associates with the excessively stimulated ERK1 /2 signal pathway by OXA.