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Akt/mTOR信号通路在氨甲酰促红细胞生成素促进脑梗死后神经发生作用的研究 预览

The role of Akt/mTOR signaling pathway in neurogenesis induced by carbamylated erythropoietin within subventricular zone after ischemic stroke
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摘要 目的探讨Akt/mTOR信号通路在氨甲酰促红细胞生成素(carbamylated erythropoietin,CEPO)促进脑梗死后室管膜下区(subventricular zone,SVZ)神经发生的作用。方法按随机数字表法将雄性小鼠分为Sham组、MCAO组、CEPO组和GSK2141795(Akt阻断剂)组。运用线栓法制作小鼠大脑中动脉闭塞模型。用改良的神经功能评分评价神经功能恢复状况。用5-溴-2-脱氧尿嘧啶核苷(5-bromo-2-deoxyuridine,BrdU)标记增殖细胞,巢蛋白(Nestin)标记神经干细胞,应用免疫荧光技术观察各组小鼠SVZ中BrdU^+/Nestin^+细胞的表达情况,Western blot技术测定各组小鼠SVZ内p-Akt和p-mTOR蛋白表达量的变化情况。结果GSK组小鼠在各评估时间点神经功能评分分值较CEPO组显著提高,差异有统计学意义(P<0.05)。术后7 d,GSK组小鼠SVZ中BrdU^+/Nestin^+细胞数,p-Akt和p-mTOR蛋白表达量较CEPO组显著减少(P<0.05)。结论CEPO可促进脑梗死后SVZ内神经干细胞增殖,这一过程可能是通过Akt/mTOR信号通路完成的。 Objective To explore the effect of Akt/mTOR signaling pathway in neurogenesis motivated by carbamylated erythropoietin(CEPO)in the subventricular zone(SVZ)after cerebral ischemia.Methods Mice were divided into four groups at random:sham-operated mice treated with vehicle(Sham),middle cerebral artery occlusion(MCAO)-operated mice treated with vehicle(MCAO),MCAO mice treated with CEPO(CEPO),and MCAO mice treated with CEPO and Akt inhibitor GSK2141795(GSK2141795).Mice were subjected to the MCAO model of ischemic stroke by thread-occlusion method.The neurological functional outcome of the mice was measured by modified neurological severity score(mNSS).Proliferative cells were labeled with 5-bromo-2-deoxyuridine(BrdU),and neural stem cells(NSCs)were labeled with Nestin.The number of BrdU^+/Nestin^+in the SVZ was measured using immunofluorescence.The expression of p-Akt and p-mTOR in the SVZ was quantified by Western blot.Results GSK2141795 group showed markedly worse performance in the mNSS test than CEPO group(P<0.05).GSK2141795 significantly reduced the number of BrdU^+/Nestin^+cells and the expression of p-Akt and p-mTOR in mice than those in the CEPO group(P<0.05).Conclusion CEPO may regulate neurogenesis in SVZ via Akt/mTOR signaling pathway after cerebral infarction.
作者 李洋 闫保君 LI Yang;YAN Baojun(Department of Interventional Neuroradiology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)
出处 《中风与神经疾病杂志》 CAS 2019年第6期509-512,共4页 Journal of Apoplexy and Nervous Diseases
关键词 氨甲酰促红细胞生成素 Akt/mTOR信号通路 室管膜下区 脑卒中 神经发生 Carbamylated erythropoietin Akt/mTOR Subventricular zone Stroke Neurogenesis
作者简介 通讯作者:闫保君,E-mail:303035716@qq.com.
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