The Role And Relationship Of Caveolin-3and COX-2in The Protection Of Sevoflurane Preconditioning On Myocardial Ischemic Reperfusion Injury

[Objective]:Observed the role and relationship of Caveolin-3and COX-2in the protective effect of sevoflurane preconditioning on myocardial ischemic reperfusion injury.[Methods]:The experiment using male Cav-3knockout (Cav-3KO) mice, along with each group’s respective wild-type (WT) littermates. They were both randomly divided into three groups:Sham group (Sham operation group); MI/R group(Myocardial ischemic reperfusion group):ligation the left coronary artery ischemia in30min then reperfusion;SP group(Sevoflurane preconditioning group):they were exposed to3cycles of10-minute exposure to2%sevofurane interspersed with15minutes of washout before subjected to ischemic reperfusion.Detected the expression of COX-2after myocardial reperfusion commenced for6hours by western blot method, measured the level of caspase3after myocardial reperfusion commenced for9hours,left ventricular end diastolic pressure and myocardial infarction area.[Result]:1.The role of caveolin-3in sevoflurane preconditionig attenuates myocardial infarction area:In the Wild type mice,Compared with control, myocardial infraction area were significantly increased in MI/R group (P<0.01).Compared with MI/R group,Sevoflurane pretreatment reduced the infraction area significantly (P<0.01).But the protective effect of sevoflurane is lost in caveolin-3gene knockout mice(P>0.05).2.The role of caveolin-3in sevoflurane preconditionig improves cardiac function:In the Wild type mice,Compared with control, left ventricular end diastolic pressure were significantly increased in MI/R group (P<0.01).Compared with MI/R group,Sevoflurane pretreatment reduced the left ventricular end diastolic pressure significantly (P<0.01).But the protective effect of sevoflurane is lost in caveolin-3gene knockout mice (P>0.05).3.The role of caveolin-3in sevoflurane preconditionig decreases apoptotic cell death: In the Wild type mice,Compared with control, Caspase3activation (determin apoptotic cell death)was significantly increased in MI/R group (P<0.01).Compared with MI/R group,Sevoflurane pretreatment reduced Caspase3activation significantly (P<0.01).But the protective effect of sevoflurane is lost in caveolin-3gene knockout mice (P>0.05).4. Sevoflurane attenuates COX-2production in a Cav-3dependent manner: In the Wild type mice.Compared with control, the expression level of COX-2was significantly increased in MI/R group (P<0.01).Compared with MI/R group,Sevoflurane pretreatment reduced COX-2significantly (P<0.01).But the protective effect of sevoflurane is lost in caveolin-3gene knockout mice (P>0.05).[Conclusion]:Sevoflurane preconditioning protects against myocardial ischemia/reperfusion via caveolin-3.And the mechanism of the protective effect could be related to inhibit COX-2expression depend on caveolin-3.