Effects of sevoflurane postconditioning on the expressions of AKT/GSK3β/mTOR during ischemia-reper-fusion in rat hearts / 临床麻醉学杂志

ABSTRACT

Objective To investigate the role of AKT/GSK3β/mTOR signaling molecule in myocardial protection of sevoflurane postconditioning.Methods Thirty-nine male Sprague-Dawley rats,weighing 200-250 g,installed in vivo myocardial ischemia-reperfusion model by left anterior de-scending coronary occlusion for 30 min.Rat hearts were randomly divided into 3 groups (n = 13 )sham control group (group Sham),purely ischemia-reperfusion group (group IR),sevoflurane post-conditioning group (group SPC).With the exception of group Sham,each group was subjected to oc-clusion for 30 min followed by 2 h reperfusion.Group SPC was subjected to sevoflurane postcondi-tioning2.4% sevoflurane was inhaled for 1 5 min starting from the end of ischemia until 1 5 min after beginning of reperfusion,while 33% oxygen was inhaled in the other groups.At the end of 2 h reper-fusion,cardiac function was evaluated by two-dimensional echocardiography,myocardial infarction size was measured by using 1% 2,3,5-triphenyltetrazolium chloride triazole (TTC),myocardial ultra-structural alterations was detected by transmission electron microscopy (TEM),cardiomyocytes ap-optosis was examined by terminal deoxynucleotidyl nickend labeling (TUNEL),the expressions of p-AKT/t-AKT, p-GSK3β/t-GSK3β, p-mTOR/t-mTOR,Bcl-2 and Bax proteins was measured by Western blot.Results Compared with group Sham,cardiac function was deteriorated,myocardial in-farct size was increased,cardiomyocyte mitochondrial damage was increased,positive apoptotic car-diomyocyte was increased,the expression of Bcl-2 was down-regluated,and the expressions of p-AKT/t-AKT,p-GSK3β/t-GSK3β,p-mTOR/t-mTOR and Bax were up-regluated in group IR (P <0.05).Compared with group IR,cardiac function was improved,myocardial infarct size was de-creased,cardiomyocyte mitochondrial damage was decreased,positive apoptotic cardiomyocyte was decreased,the expression of Bax was down-regluated,and the expressions of p-AKT/t-AKT,p-GSK3β/t-GSK3β,p-mTOR/t-mTOR and Bcl-2 were up-regluated in group SPC (P < 0.05 ). Conclusion Sevoflurane postconditioning can mitigate ischemia-reperfusion injury to in vivo rat hearts,decreased cardiomyocyte mitochondrial damage,inhibited cardiomyocyte apoptosis,and its mechanism was related to the activation of AKT/GSK3β/mTOR signaling molecule.