Abstract: 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 2h and reperfusion 24h. Rats were randomly divided into Sham group (Sham), 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 reduce 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 might increase the proliferation of neurons and improve the cerebral blood glucose concentration.

Key words: Orexin-B, brain ischemia-reperfusion, neuroprotection, phosphorylation of protein kinase b, glycogen synthase kinase 3β