摘要Background:It is well documented that sevoflurane postconditioning (SP) has a significant myocardial protection effect.However,the mechanisms underlying SP are still unclear.In the present study,we investigated the hypothesis that the Pim-1 kinase played a key role in SP-induced cardioprotection by regulating dynamics-related protein 1 (Drp 1).Methods:A Langendorff model was used in this study.Seventy-two rats were randomly assigned into six groups as follows:CON group,ischemia reperfusion (I/R) group,SP group,SP+proto-oncogene serine/threonine-protein kinase 1 (Pim-1) inhibitor Ⅱ group,SP+dimethylsufoxide group,and Pim-1 inhibitor Ⅱ group (n =12,each).Hemodynamic parameters and infarct size were measured to reflect the extent of myocardial UR injury.The expressions of Pim-1,B-cell leukemia/lymphoma 2 (Bcl-2) and cytochrome C (Cyt C) in cytoplasm and mitochondria,the Drp 1 in mitochondria,and the total Drp1 and p-Drp 1 ser637 were measured by Western blotting.In addition,transmission electron microscope was used to observe mitochondrial morphology.The experiment began in October 2014 and continued until July 2016.Results:SP improved myocardial I/R injury-induced hemodynamic parametric changes,cardiac function,and preserved mitochondrial phenotype and decreased myocardial infarct size (24.49 ± 1.72％ in Sev group compared with 41.98 ± 4.37％ in I/R group;P ＜ 0.05).However,Pim-1 inhibitor Ⅱ significantly (P ＜ 0.05) abolished the protective effect of SP.Western blotting analysis demonstrated that,compared with I/R group,the expression of Pim-1 and Bcl-2 in cytoplasm and mitochondria as well as the total p-Drp1ser637 in Sev group (P ＜ 0.05) were upregulated.Meanwhile,SP inhibited Drp 1 compartmentalization to the mitochondria followed by a reduction in the release ofCyt C.Pretreatment with Pim-1 inhibitor Ⅱ significantly (P ＜ 0.05) abolished SP-induced Pim-1/p-Drp 1 ser637 signaling activation.Conclusions:These findings suggested that SP could attenuate myocardial ischemia-reperfusion injury by increasing the expression of the Pim-1 kinase.Upregulation of Pim-1 might phosphorylate Drp 1 and prevent extensive mitochondrial fission through Drp 1 cytosolic sequestration.