氨甲酰化促红细胞生成素经PI3-K/Akt信号通路抗脑缺血损伤

摘要

目的 观察脑缺血后氨甲酰化促红细胞生成素(CEPO)的神经保护作用并探讨其可能机制.方法 健康雄性SD大鼠随机分为6组(n=10):(1)假手术组;(2)缺血组;(3)EPO组;(4)CEPO组;(5)LY(LY294002)组;(6)CEPO+LY组.应用大脑中动脉线栓法(MCAO)制作大鼠局灶性脑缺血模型,评定大鼠神经功能并计算脑梗死体积,Western blot 方法检测PI3-K/Akt活性变化.结果 EPO组与CEPO组脑梗死体积均明显缩小,神经功能显著改善,磷酸化Akt(pAkt)水平明显增高,且两组之间无明显差异,但CEPO的神经保护作用及对Akt磷酸化的诱导效应均可被PI3-K抑制剂 LY294002部分抵消.结论 CEPO具有与EPO相当的缺血后脑保护作用,其机制可能与PI3-K/Akt信号通路激活有关.%Objective To study the neuroprotective effect of carbamylated erythropoietin (CEPO) on cerebral ischemic injury and its possible mechanism.Methods Sixty healthy male SD rats were randomly divided into 6 groups (n=10 each):sham operation group,ischemia group,EPO group,CEPO group,LY group and CEPO+LY group.Focal cerebral ischemia model of middle cerebral artery occlusion (MCAO) was established in rats using the suture method.Neurological function and the volume of cerebral infarction were evaluated on the expected time points.The changes in activity of PI3-K/Akt pathway were determined by Western blot.Results In both EPO group and CEPO group,the protein levels of phosphorylated Akt (pAkt) were increased markedly with less volume of cerebral infarction and better neurological function,and there was no significant difference between the two groups.However,the neuroprotection of CEPO and its induction of Akt phosphorylation were partially abolished by LY294002,which was the inhibitor of PI3-K.Conclusion The neuroprotective effect of CEPO is equivalent to EPO after cerebral ischemia,which may be related to the activation of PI3-K/Akt signaling pathway.