Résumé
Objective To evaluate the role of TWIK-related K+ channel 1 (TREK-1) in reduction of cerebral ischemia-reperfusion (I/R) injury by sevoflurane preconditioning in mice.Methods Sixty male Kunming mice,aged 8 weeks,weighing 21-29 g,were randomly divided into 5 groups (n=12 each) using a random number table:sham operation group (group S),group I/R,sevoflurane preconditioning group (group SP),TREK-1 small hairpin RNA (shRNA) lentivirus + sevoflurane preconditioning group (group TSP),and negative control shRNA lentivirus + sevoflurane preconditioning group (group NSP).In S,I/R and SP groups,normal saline 15 μl was injected into the lateral cerebral ventricle at 1 μl/min.In TSP and NSP groups,TREK-1 shRNA lentivirus and negative control shRNA lentivirus 15 μl were injected into the lateral cerebral ventricle,respectively,at a rate of 1 μl/min.And 14 days later,S and I/R groups inhaled 100％ oxygen for 60 min,SP,TSP and NSP groups inhaled 2.4％ sevoflurane for 60 min,followed by 15 min washout by inhaling 100％ oxygen,and then cerebral I/R was produced by occlusion of right internal carotid artery for 2 h followed by reperfusion.At 24 h of reperfusion,neurological deficit was scored (NDS).The mice were then sacrificed,and brains were removed to determine the cerebral infarct size (IS),expression of hippocampal caspase-3 and cell apoptosis in brain tissues.Apoptosis index (AI) was calculated.Results Compared with group S,the NDS,cerebral IS,expression of hippocampal caspase-3 and AI were significantly increased in I/R,SP,TSP and NSP groups.Compared with group I/R,the NDS,cerebral IS and AI were significantly decreased,and the expression of hippocampal caspase-3 was down-regulated in SP,TSP and NSP groups.Compared with group SP,the NDS,cerebral IS and AI were significantly increased,and the expression of hippocampal caspase-3 was up-regulated in group TSP,and no significant change was found in the parameters mentioned above in NSP group.Conclusion Sevoflurane preconditioning reduces cerebral I/R injury through activating TREK-1 and inhibiting apoptosis in hippocampal neurons of mice.