Role of HIF-1α in reduction of apoptosis in cortical neurons of rats by sevoflurane preconditioning: the relationship with Bid, Bim and Puma / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of hypoxia inducible factor-1α (HIF-1α) in reduction of apoptosis in cortical neurons of rats by sevoflurane preconditioning.Methods Primary cortical neurons obtained from neonatal Sprague-Dawley rats were seeded in 6-well plates (2 ml/well),and randomly divided into 4 groups (n =15 each) using a random number table:control group (C group),anoxiareoxygenation (A/R) group,sevoflurane preconditioning group (SP group) and HIF-1α inhibitor 2-methoxyestradiol group (H group).The neurons were subjected to O2-glucose deprivation for 90 min followed by restoration of O2-glucose supply for 24 h.In group SP,the neurons were exposed to 2.0％ sevoflurane for 2 h followed by 5 min washout for 3 times,and then sevoflurane preconditioning was performed immediately.In group H,sevoflurane preconditioning was performed at 72 h of incubation with 5 μmol/L 2-methoxyestradiol.The apoptosis in neurons was assessed using Annexin V-FITC/PI assay,and apoptosis rate was calculated.The expression of Bid,Bim,Puma and activated caspase-3 in neurons was detected by Western blot.Results Compared with group C,apoptosis rate was significantly increased,and the expression of Bid,Bim,Puma and activated caspase-3 was up-regulated in group A/R.Compared with group A/R,apoptosis rate was significantly decreased,and the expression of Bid,Bim,Puma and activated caspase-3 was down-regulated in group SP.Compared with group SP,apoptosis rate was significantly increased,and the expression of Bid,Bim,Puma and activated caspase-3 was up-regulated in group H.Conclusion HIF-1α mediates reduction of apoptosis in rat neurons by sevoflurane preconditioning,and down-regulated expression of Bid,Bim,and Puma is involved in the mechanism.