Ephrinb1-EphB2-Map2信号通路在柚皮素促进脑缺血后海马神经发生中的作用

Hippocampal neurogenesis after cerebral ischemia induced by naringenin by ephrinb1-EphB2-Map2 pathway

目的探讨柚皮素(NAR)对脑缺血小鼠内源性海马神经发生的改善作用及可能机制。方法双侧颈总动脉夹闭法建立急性脑缺血模型;HE染色检测病理变化;Morris水迷宫评估认知功能;免疫荧光观察神经发生;RT-PCR和Western blotting检测海马ephrinb1、EphB2、Map-2表达。结果与假手术组相比,模型组小鼠脑缺血后海马CA1区锥体神经元损伤(P<0.01),学习记忆功能下降(P<0.01),这些结果提示,小鼠出现了脑缺血损伤。同时,模型组小鼠BrdU、DCX、BrdU/NeuN阳性表达增加(P<0.01),提示脑缺血后海马区出现神经发生。与模型组相比,NAR治疗后小鼠CA1区病理损伤改善,学习记忆能力提高,神经发生进一步得到促进。同时,海马ephrinb1、EphB2、Map-2的mRNA和蛋白表达水平分别上调(P<0.05)。结论NAR可促进脑缺血后海马神经发生,改善认知功能,其机制可能与ephrinb1/EphB2/Map-2通路的激活有关。

Objective To investigate the ameliorating effect of naringenin(NAR)on endogenous hippocampal neurogenesis in mice with cerebral ischemia and its possible mechanism.Methods The Model of CI(cerebral ischemia)was established by bilateral common carotid artery occlusion(BCCAO);The pathological changes were detected by HE staining;The learning and memory functions were assessed by Morris water maze;The positive expression of BrdU,DCX and BrdU/NeuN was observed through immunofluorescence staining for detect hippocampal neurogenesis;The expressions of ephrinb1,EphB2,Map-2 were detected by RT-PCR and Western blotting,respectively.Results Compared with the Sham group,the pyramidal neurons in the hippocampal CA1 region were significantly damaged(P<0.01)and the learning and memory function was significantly decreased(P<0.01)after cerebral ischemia,suggesting that mice have cerebral ischemic injury.Meanwhile,the positive expression of BrdU,DCX and BrdU/NeuN in hippocampus of the model group was significantly increased,indicating that neurogenesis occurred in hippocampus after cerebral ischemia(P<0.01).Compared with the model group,the pathological damage in CA1 region could be significantly improved,learning and memory ability was significantly improved,and neurogenesis was further promoted after naringenin treatment.At the same time,the mRNA and protein expressions of ephrinb1,EphB2,Map-2 were up-regulated(P<0.05).Conclusion Naringenin could promote hippocampal neurogenesis and improve cognitive function after cerebral ischemia,which may be related to ephrinb1/EphB2/Map-2 signaling pathway.