Background:Sevoflurane preconditioning (SP) has been shown to invoke potent myocardial protection in animal studies and clinical trials.However,the mechanisms underlying SP are complex and not yet well understood.We investigated the hypothesis that the cardioprotection afforded by SP is mediated via the Wnt/glycogen synthase kinase 3β3 (GSK3β)/β-catenin signaling pathway.Methods:Two models were established:A Langendorffperfused rat heart model and the H9C2 cell hypoxia/reoxygenation model.Both rats and H9C2 cells were randomly divided into 6 groups as follows:S group,ischemia-reperfusion (I/R) group,DMSO group,IWP group,SP group,and SP + IWP group.Hemodynamic parameters,lactate dehydrogenase (LDH) activity in coronary effluent and cell culture supatant,and the infarct size were measured to evaluate myocardial ischemia-reperfusion injuries.To determine the activity of Wnt/GSK3β/β-catenin signaling pathway,the expressions ofWnt3a,phospho-GSK3β,and β-catenin were measured by West blotting.Results:SP improved cardiac function recovery,reduced infarct size (18 ± 2％ in the SP group compared with 35 ± 4％ in the I/R group;P ＜ 0.05),decreased LDH activity in coronary effluent,and culture supatant.IWP-2,an inhibitor of Wnt,abolished the cardioprotection by SP.In addition,West blotting analysis demonstrated that the expressions ofWnt3a,phospho-GSK3β,and β-catenin significantly (P ＜ 0.05) increased in the I/R group,compared with the S group;and compared to I/R group,SP significantly (P ＜ 0.05) increased Wnt3a,phospho-GSK3β,and β-catenin expressions.Pretreatment with IWP-2 significantly (P ＜ 0.05) abolished SP-induced Wnt/GSK3 β/β-catenin signaling activation.Conclusions:The results showed for the first time that cardioprotection afforded by SP may be mediated partly via the Wnt/GSK3β/β-catenin signaling pathway.