A Study On Minocycline Can Protects Rat Brain From Chronic Cerebral Ischemia By Notch Signaling Pathway

Background: Cerebrovascular disease is a serious threat to human health,which ischemic disease is the most common.The study of its pathogenesis and treatment targets will greatly reduce the disability and mortality of cerebrovascular diseases.Objective: To observe whether minocycline can exert cerebral protective effect by regulating Notch signaling pathway after chronic cerebral ischemia.Methods: Forty healthy male Sprague-Dawley rats were randomly divided into 5 groups(n=8): Sham operation group,Ischemia model group,DAPT inhibitor group,Minocycline treatment group,DAPT+minocycline group.The model of chronic cerebral ischemia was established by permanent bilateral common carotid artery ligation(2-VO).Except that the bilateral common carotid arteries were not ligated,the other operations of sham operation group are the same as model group.The administration will be done 1 month after the model established.The Sham operation group and the Ischemic model group ware given intragastric administration of equal volume of normal saline,DAPT inhibitor group was given the DAPT(intraperitoneal injection of 10μmol/kg,administration once weekly,the other treatments were the same as those in the Ischemic model group),Minocycline treatment group was intragastrically administered with 50 mg/kg minocycline,and DAPT+minocycline group was administered: Based on the DAPT inhibitor group above,50 mg/kg minocycline was given intragastrically.After 4 weeks of feeding,the rats were tested for learning and memory abilities.Morris water maze(MWM)experiments were performed to determine the length of the escape latency and the number of crossings of the original platform area.At the end of the MWM experiment,the hippocampal tissue of rats ware taken,then immunohistochemistry and Western blot were performed to detect the expression of Hes1 downstream of VEGF and Notch signaling pathway.Results: 1.Compared with sham operation group,the learning and memory abilities of the model group decreased(P<0.05).2.Minocycline treatment group were respectively compared with the model group and the DAPT + minocycline group,DAPT+minocycline group was compared with DAPT inhibitor group show that the ability of learning and memory of learning was increased(P<0.05).3.Compared with DAPT inhibitor group,the expression of VEGF and Hes1 were significantly different in minocycline treatment group(P<0.05).4.Minocycline treatment group were respectively compared with the model group and the DAPT + minocycline group,DAPT+minocycline group was compared with DAPT inhibitor group show that the expression of VEGF and Hes1 was increased(P<0.05).Conclusion: Minocycline can promote angiogenesis by regulating Notch signaling pathway in the brain of chronic cerebral ischemia rats,and then exerts neuroprotective effect.