Role of hypoxia-inducible factor-1α in sevoflurane postconditioning-induced reduction of myocardial ischemia-reperfusion injury in mice

Abstract

Objective To evaluate the role of hypoxia-inducible factor-1α(HIF-1α) in sevoflurane postconditioning-induced reduction of myocardial ischemia-reperfusion (I/R) injury in mice. Methods Forty pathogen-free healthy male C57 mice, aged 8 weeks, weighing 20-30 g, were assigned into 4 groups (n=10 each) using a random number table: sham operation group(group Sham), myocardial I/R group (group I/R), sevoflurane postconditioning group (group SPC) and HIF-1α inhibitor 2Me2 group (group 2Me2). Myocardial I/R was induced by occlusion of the left anterior descending branch of the coronary artery for 30 min followed by 120 min of reperfusion in pentobarbital sodium-anesthetized mice.In group SPC, 3% sevoflurane was inhaled for 15 min starting from the onset of reperfusion.In group 2Me2, 30% 2Me2 (30 mg/kg) was intraperitoneally injected at 30 min before ischemia.The mice were sacrificed at the end of reperfusion, and the hearts were removed for determination of the myocardial infarct size (using the Image J software) and expression of HIF-1α in the nucleus of cardiomyocytes (by Western blot). Results Compared with group Sham, the myocardial infarct size was significantly increased in I/R, SPC and 2Me2 groups, the expression of HIF-1α was significantly up-regulated in I/R and SPC groups, and the expression of HIF-1α was significantly down-regulated in group 2Me2 (P<0.05). Compared with group I/R, the myocardial infarct size was significantly decreased, and the expression of HIF-1α was up-regulated in group SPC, and the myocardial infarct size was significantly increased, and the expression of HIF-1α was down-regulated in group 2Me2 (P<0.05). Compared with group SPC, the myocardial infarct size was significantly increased, and the expression of HIF-1α was down-regulated in group 2Me2 (P<0.05). Conclusion The mechanism by which sevoflurane postconditioning reduces myocardial I/R injury is related to up-regulation of HIF-1α expression in mice. Key words: Hypoxia-inducible factor 1, alpha subunit; Anesthetics, inhalation; Myocardial reperfusion injury; Ischemic postconditioning