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 artery occlusion,MCAO） was established which has been ischemic 2 h and reperfusion 24 h. Rats were randomly divided 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 2 as 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.
出处
《基础医学与临床》
CSCD
2018年第3期340-343,共4页
Basic and Clinical Medicine
基金
国家自然科学基金青年科学基金(81501018)
山东省自然科学基金(ZR2015CL021)
