Role of HIF-1α/BNIP3 signaling pathway in sevoflurane-induced attenuation of myocardial ischemia-reperfusion injury in rats: relationship with autophagy / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of hypoxia-inducible factor-1α (HIF-1α)/Bcl-2/E1B-19kDa interacting protein 3 (BNIP3) signaling pathway in sevoflurane-induced attenuation of myocardial ischemia-reperfusion (I/R) injury in rats and the relationship with autophagy.Methods:Ninety healthy adult male Sprague-Dawley rats, weighing 300-350 g, were randomly divided into 5 groups ( n=18 each) sham operation group (Sham group), I/R group, sevoflurane group (SEV group), HIF-1a inhibitor 2ME2 group (2ME2 group), and 2ME2+ sevoflurane group (MSP group). Myocardial I/R injury model was established by ligating the left anterior descending branch of coronary artery for 40 min followed by 120-min reperfusion in anesthetized rats.In SEV group, 2.4% sevoflurane was inhaled for 15 min starting from the beginning of reperfusion.In 2ME2 group and MSP group, 2ME2 (15 mg/kg) was intraperitoneally injected at 1 h before ligation of the left anterior descending branch of coronary artery, and the other treatments were similar to those previously described in group I/R or in group SEV.Animals were sacrificed at 120 min of reperfusion, and the left ventricular myocardium was taken for determination of the expression of HIF-1α and BNIP3 (by Western blot), activity of ROS (by DHE), and myocardial infarct size (by TTC)and for observation of autophagosome (with an electron microscope). Results:Compared with Sham group, the activity of ROS, the number of autophagosome and myocardial infarct size were significantly increased in the other four groups, the expression of HIF-1α and BNIP3 was up-regulated in I/R group and SEV group ( P<0.05). Compared with I/R group, the activity of ROS, the number of autophagosome and myocardial infarct size were significantly decreased in the other four groups, the expression of HIF-1α and BNIP3 was up-regulated in SEV group, and no significant difference was found in the activity of ROS, the number of autophagosome or myocardial infarct size ( P>0.05), and the expression of HIF-1α and BNIP3 was down-regulated in 2ME2 and MSP groups ( P<0.05). Compared with SEV group, the activity of ROS, the number of autophagosome and myocardial infarct size were significantly increased, and the expression of HIF-1α and BNIP3 was down-regulated in 2ME2 and MSP groups ( P<0.05). Conclusion:HIF-1α/BNIP3 signaling pathway is involved in sevoflurane-induced attenuation of myocardial I/R injury, which is related to inhibiting autophagy in rats.