Sevoflurane Preconditioning Plays A Protective Role In Cerebral/ischemia Reperfusion Injury Through Adiponectin

In cerebrovascular diseases,stroke is the main cause of death and disability.Most of them are patients with ischemic stroke.The treatment of ischemic stroke is usually intravascular or thrombolytic therapy and these treatments may cause cerebral/ischemia-reperfusion(CI/R)injury and seriously affect the therapeutic effect.Therefore,how to alleviate cerebral ischemia/reperfusion injury is an urgent scientific problem in the field of cerebrovascular diseases.Basic and clinical studies have shown that sevoflurane pretreatment can reduce CI/R injury,but how sevoflurane affects and regulates the molecular mechanism in vivo to play a brain protective role has not been fully clarified.Adiponectin is a polypeptide adipokine secreted from adipose tissue in blood.It has a variety of biological functions such as protecting vascular endothelium and anti-inflammatory.In the case of CI/R,it will lead to the destruction of blood-brain barrier and the death of endothelial cells.APN leaks out from the vascular space and accumulates in the damaged area of ischemia-reperfusion,increasing the concentration of plasma APN in the damaged area and exerting brain protective effect.At present,the factors affecting the brain protection of adiponectin and its signal pathway in vivo are unknown.This study intends to clarify whether sevoflurane can reduce ischemia-reperfusion injury by increasing the level of plasma adiponectin,and then improve brain function after ischemia-reperfusion.The completion of this study will provide a new theoretical basis for the brain protective mechanism of volatile anesthetics and provide theoretical support for their wide clinical application.Objective:In this study,the effects of sevoflurane preconditioning on CI/R in mice and its mechanism were determined by knocking out adiponectin and To observe the differences of cerebral infarction size,nerve cell apoptosis level,plasma adiponectin level and brain cognitive function in cerebral ischemia/reperfusion model mice pretreated with sevoflurane.To understand whether adiponectin is the key to the protective effect of sevoflurane preconditioning on CI/R injury,so as to further understand the mechanism of brain protective effect of sevoflurane preconditioning,and provide ideas for clinical prevention of CI/R injury.Methods:(1)Grouping: Wild type(C57BL / 6)and adiponectin gene knockout(KO)mice :Sham-Control group,Sham-Sevopre group,CI/R-Control group and CI/R-Sevopre group.(2)The cerebral infarction area of 8 groups of mice was observed by TTC staining;(3)The motor Behavioral indicators of 8 groups of mice were observed by water maze method;(4)The expression levels of apoptotic factors caspase 3,bax and chop were detected by Western blotting;(5)The expression level of adiponectin in plasma was measured by ELISA kit.Results:(1)24 hours after CI/R operation,the brain tissues of 8 groups of mice were taken out for TTC staining.The staining results showed that there was a significant difference in gray infarct area between WT-CI/R-Control group and WT-Sham-Control group(P < 0.05),indicating that the modeling was successful.After pretreatment,the infarct area in WT-CI/R-Sevopre group group decreased compared with WT-CI/R-Control group(P < 0.05);There was no difference in infarct area between KO-CI/R-Control group and KO-CI/R-Sevopre group,and the protective effect of sevoflurane decreased(P > 0.05);(2)The water maze data of 8 groups of mice after CI/R showed that in the wild group,the latency time of WT-CI/R-Control group was significantly increased.Compared with WT-Sham-Control group(P < 0.05),after sevoflurane pretreatment,the latency of WT-CI/R-Sevoopre group was significantly shorter than that of WT-CI/R-Control group(P < 0.05);In the adiponectin knockout mice group,the protective effect of sevoflurane was weakened,and there was no significant difference in latency between KO-CI/R-control group and KO-CI/R-Sevopre group(P > 0.05)(3)Compared with WT-Sham-Control group,the contents of apoptotic factors caspase 3,bax and chop protein in WT-CI/R-Control group increased significantly after CI/R operation,and the protein expression decreased after sevoflurane pretreatment.There was no difference in caspase 3,bax and chop between KO-CI/R-Control group and KO-CI/R-Sevopre group;(4)The plasma adiponectin level of ELISA showed that the adiponectin level decreased after modeling,and the adiponectin level increased significantly after sevoflurane-pretreatment.Conclusion:The results showed that sevoflurane pretreatment significantly reduced the area of cerebral infarction and brain cell apoptosis,so as to improve brain cognitive function.In addition,the protective effect is weakened after adiponectin knockout.