Effects of sevoflurane postconditioning on mitophagy during ischemia-reperfusion in rats

Objective To evaluate the effects of sevoflurane postconditioning on mitophagy during myocardial ischemia-reperfusion (I/R) in rats. Methods Forty-two pathogen-free adult male Sprague-Dawley rats, weighing 250-300 g, were randomly divided into 3 groups (n= 14 each) using a random number table: sham operation group (group S), I/R group and sevoflurane postconditioning group (group SP). Myocardial I/R was induced by 30 min ligation of the left anterior descending branch of the coronary artery followed by 2 h of reperfusion.In group SP, 2.4% sevoflurane was inhaled for 15 min starting from the onset of reperfusion, while 33% oxygen was inhaled in group I/R.The rats were sacrificed at the end of reperfusion, and the hearts were removed for measurement of myocardial infarct size (by 1% 2, 3, 5 triphenyltetrazolium chloride), expression of LC3Ⅱ/LC3Ⅰ, Beclin-1, p62 and Parkin (by Western blot), and mitochondrial membrane potential (by using JC-1 probe), and for examination of the ultrastructure of cardiomyocytes (with transmission electron microscope). Results Compared with group S, the myocardial infarct size was significantly increased, mitochondrial membrane potential was decreased, the expression of LC3Ⅱ/LC3Ⅰ, Beclin-1 and Parkin was up-regulated, and the expression of p62 was down-regulated in group I/R.Compared with group I/R, the myocardial infarct size was significantly decreased, the mitochondrial membrane potential was increased, and the expression of LC3Ⅱ/LC3Ⅰ, Beclin-1, p62 and Parkin was down-regulated in group SP. Conclusion Sevoflurane postconditioning can mitigate I/R injury in rats, and inhibition of excessive activation of mitophagy may be involved in the mechanism. Key words: Anesthetics, inhalation; Myocardial reperfusion injury; Mitochondria; Autophagy; Postconditioning