An Experimental Study Of Orexin-B Protecting Function For The Cerebral Ischemia Reperfusion Injury In Rats

Background:Stroke is one of the important cerebrovascular diseases that seriously threatens human health.Ischemic stroke is most commonly seen and its morbidity and mortality are high in the worldwide.Early intravenous thrombolysis and endovascular treatment are effective in clinical practice,but the secondary neurological damage caused accompanying by ischemia-reperfusion significantly affects the prognosis of recovery.The popularization and application of thrombolysis and thrombectomy are also affected.The current research shows that secondary neuronal injury after cerebral ischemia-reperfusion is closely related to endoplasmic reticulum stress,inflammatory response,energy metabolism,excitatory amino acids and so on.Therefore,intervening in all aspects of different mechanisms of injury may provide new and effective ways to treat ischemic stroke.Orexin B,a neuropeptide secreted mainly by the hypothalamus,is an endogenous ligand for GPCR.Studies have shown that orexin B can inhibit spontaneous programmed death of dopaminergic neuron and thus protects the neuron.However,whether orexin B can inhibit neuronal injury caused by cerebral ischemia-reperfusion and exert neuroprotection or not,and its possible functional mechanism needs further to be investigated.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 had been ischemic 2h and reperfusion 24h.Rats were randomly divided into control 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 expression of Orexin receptor 2,p-AKT,and p-GSK-3? proteins in hippocampus was detected.Jumping test was used to detect learning and memory abilities in rats.Results:Orexin-B significantly reduced the volume of cerebral infarction through TTC staining.In Orexin-B group,the expression of Orexin Receptor 2 as well as p-AKT and p-GSK-3? was significantly increased(P<0.05).Furthmore,in the Orexin-B treated group,Orexin-B could improve the latency period and decline the mistakes through rat Jumping test(P<0.05).Conclusions:The neuroprotective effect of Orexin-B in cerebral ischemia-reperfusion injury may enhance p-AKT and p-GSK-3? activity,which might increase the restoration of neurons and promoting the survival of neurons concentration.