食欲素-B抑制大鼠脑缺血再灌注损伤

摘要

目的 研究食欲素-B(orexin-B,OXB)对大鼠脑缺血再灌注的神经保护作用及其分子机制.方法 制备大鼠大脑中动脉栓塞模型(MCAO),将大鼠随机分为:假手术组(control)、缺血再灌注组(I/R)、缺血再灌注+PBS 组(I/R+PBS)和缺血再灌注+orexin-B组(I/R+OXB);通过神经功能评分确定模型是否成功;TTC染色法测定大鼠脑梗死体积;Western blot检测海马区食欲素受体2(OX2R)、p-AKT和p-GSK-3β蛋白表达;跳台实验检测大鼠学习与记忆.结果 I/R组海马中OX2R及p-AKT蛋白表达较对照组减少(P<0.05),p-GSK-3β蛋白表达增加(P<0.05),而I/R+OXB组上述变化明显减轻(P<0.05);I/R+OXB组脑梗死体积明显减少,I/R组潜伏期时间减少,错误次数增多(P<0.05),而I/R+OXB组上述变化显著减小(P<0.05).结论 食欲素-B抑制脑缺血再灌注损伤,可能与增强p-AKT活性、抑制p-GSK-3β活性有关.%Objective To study the neuroprotective effect of orexin-B on rat model of cerebral ischemia-reperfusion injury and its molecular mechanism. Methods The artery occlusion model of male Wister rats(middle cerebral ar-tery occlusion,MCAO) was established which has been ischemic 2 h and reperfusion 24 h. Rats were randomly di-vided into sham group (control), ischemia-reperfusion group (I/R), ischemia-reperfusion +PBS group (I/R+PBS),and ischemia-reperfusion +orexin-B group (I/R+OXB). The neurological deficit scores were processed to inclusion and exclusion. Infarct size was determined by TTC staining;Using Western blot,the expressions of orexin receptor 2,p-AKT,p-GSK-3β proteins in hippocampus were detected;Jumping test was used to detect learning and memory abilities in rats. Results Orexin-B significantly reduced the volume of cerebral infarction in TTC staining;orexin-B group was significantly increased the expression of orexin receptor 2as well as p-AKT,which decreased p-GSK-3β (P<0.05),compared with the untreated group. Furthmore,the orexin-B treated group can improve the latency period and decline the mistakes in rat Jumping test(P<0.05). Conclusions The neuroprotective effect of orexin-B in cerebral ischemia-reperfusion injury may enhance p-AKT activity and inhibit p-GSK-3β activity,which may increase the proliferation of neurons and improve the cerebral blood glucose concentration.