| Background:Stroke has become a major killer of human health and quality of life.In China,stroke has become the first cause of death of the whole disease.Ischemic stroke accounts for more than 80% of all stroke.It is characterized by high morbidity,high rate of disability,high mortality and high recurrence rate of four.Stroke is a preventable and controllable disease.In addition to the control of primary disease,it is necessary to make an in-depth study on the occurrence and development of stroke and effective prevention and control measures.Remote preconditioning,as a new means of protection for ischemic / reperfusion injury,has attracted the attention of neuroscience.The aim of this study is to confirm the protective effect of remote ischemic preconditioning on the ischemia-reperfusion injury of the Central Nervous System(CNS),and to systematically study and analyze its neuroprotective mechanism.Ischemic preconditioning(IP)refers to the induction of initiating tissue or cellular endogenous protective mechanisms through one or more transient,sub-lethal ischemia/reperfusion,thereby increasing tolerance of organs to the fatal ischemic injury,reducing the degree of damage and extent of injury.Remote ischemic preconditioning(RIPrC)refers to the use of transient ischemia/reperfusion of an organ or tissue to produce ischemic injury to distant organs by releasing biochemical messengers or activating neural pathways in the circulation.RIPrC is non-invasive to the target organs and does not direct put the stress on the target.Therefore,it has a broad prospect of clinical application.The exact mechanism of RIPrC is not clear.It is considered that protection information is transmitted in the same organ during direct ischemic preconditioning,while RIPrC protects the information to distant organs.The transmission of information may be mediated by humoral media,neural pathways,or joint action.We found in the previous part of cerebral infarction after illness,through remote ischemic postprocessing,some inflammatory cells and inflammatory factors in peripheral blood have different degrees of change,these changes were accompanied by neurological function improvement on CNS ischemia / reperfusion injury.Therefore,we speculate that the distal ischemic treatment may affect the center by affecting the immune function of the body.Objective:We try to confirm the protective effect of RIPrC on the MCAO mouse model of ischemia and reperfusion;and to explore the protective effect of RIPrC on normal mice peripheral and central nervous system immune;through the regulation of RIPrC on cerebral ischemia and reperfusion injury of central and peripheral immune function,to investigate the cell signaling pathway related to immune regulation.Finally,we conformed the protect the effect of RIPrC by regulating the function of central and peripheral immune.Materials and methods:The experimental animal is 8-10 week,male,C57/BL6 mice weighing 20-25g;RIPrC put the stress on left lower limb,after 15 min blood reflow for a period of 15 min block,a total of 3 cycles,24 h after the onset of MCAO.We use MCAO model to creat local ischemic.Laser Doppler flowmetry was used to monitor whether the blood flow in the lower extremities was blocked and the degree of cerebral blood flow was decreased after MCAO.TTC staining was used to observe the volume of cerebral infarction.Longa score was used to measure nerve function,the corner test and the adhesive tape removal test were used to evaluate of behavior.Cytof was determinateted the peripheral blood immune cells and cell signal transduction pathway key factors.Result:(1)MCAO mice experiment to the contralateral limb corner probability increased significantly,to the tape was prolonged,and in the implementation of RIPrC,corner test steering the contralateral limb significantly reduced the chance to tape,time was shortened,and the Longa score also improved,the infarct volume was significantly reduced,indicating that RIPrC can reduce the injury and cerebral infarction the volume of motor nerve function improved significantly after cerebral ischemia.(2)Cytof results showed that remote ischemic treatment significantly increase the number of CD4+T cells,CD8+T cells,neutrophils and microglia in normal mice;Cell signal transduction pathway key factor p EGFR,i NOs,p ERK1-2,p S6,p STAT3,Gata3 and IRF4 expression in these cells was first increased and then decreased,wherase Arg-1 was significantly increased in microglia.(3)Cytof results for MCAO mice showed that RIPrC activated the immune function in cerebral ischemia reperfusion injury of peripheral,but inhibited the immune response of the central nervous system,expressed as CD4+T cells and Eff/mem CD4+T cells,CD8+T cells,Eff/mem cells and CD8+T in neutrophils and the number of microglia cells increased,CD4+T cells,Eff/mem CD4+T cells,CD8+T cells,Eff/mem CD8+T cells,neutrophils and microglia in inflammatory related cell signal transduction pathway key factor p4E-BP1,p STAT4,p STAT1,p STAT3,p-P38,i NOs and I Ba decreased significantly after treatment.While Arg-1 decreased in CD4+T cells,Eff/mem CD4+T cells and CD8+T cells,Eff/mem CD8+T cells,neutrophils,but significantly increased in microglia.Conclusion:(1)RIPrC has protective effect on ischemic and reperfusion brain injury of MCAO model in mice.(2)Remote ischemic treatment can affect the normal mouse peripheral and central nervous system immune function,the main effector cells into CD4+T cells,Eff/mem CD4+T cells,CD8+T cells,Eff/mem CD8+T cells,neutrophils,microglia,cell signal transduction may affect the path of p EGFR,i NOs,Arg-1,p ERK1-2,p S6,p STAT3 Gata3 and IRF4;(3)RIPrC put the effect on cerebral ischemia and reperfusion injury by regulating the central and peripheral immune function.RIPrC may adjust p STAT3,i NOs and Arg-1 signal transduction pathways to regulating the number of CD4+T cells,Eff/mem CD4+T cells,CD8+T cells,Eff/mem CD8+T cells,neutrophils and microglia in the state of immune environment of MCAO mice,and play a neuroprotective effect on MCAO mice. |
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