Sevoflurane Postconditioning Upregulates HIF-1α Pathway Enhances BNIP3 Mediated Mitochondrial Autophagy in Myocardium of Aged Mice

BACKGROUND: Diminished mitochondrial autophagy in aged myocardium may be due to impaired HIF-1α protein expression. Previous studies confirmed that upregulation of HIF-1α expression protects myocardial tissue from ischemia/reperfusion (I/R) injury and found that sevoflurane post-conditioning (SpostC) mediated mitochondrial autophagy plays a significant role in myocardial protection. However, the protective mechanism of SpostC in aged myocardium is unclear. This study aimed to investigate whether SpostC regulates BNIP3 - mediated mitochondrial autophagy by upregulating HIF-1α expression, thus alleviating myocardial I/R injury in aged mice.Methods: An in vivo mouse model of myocardial I/R injury was established and treated with sevoflurane at the time of reperfusion, and at the end of reperfusion, echocardiographic changes, myocardial infarct size, mitochondrial ultrastructure, and autophagosomes were measured, mitochondrial respiratory function and enzyme activity were detected, serum LDH, CKM, CK-MB, TNNT2, IL-6 levels were determined, and Western blot was used to examine the expression levels of phosphorylated HIF-1α, LC3-II, BNIP3, Beclin1, TLR9, and IL-6 protein in myocardial tissue.RESULTS: In young, healthy myocardium, SpostC upregulated the expression of HIF-1α, activated the downstream target gene BNIP3 protein, and upregulated the expression levels of autophagy essential proteins LC3-II, Beclin-1, and TLR9, attenuated myocardial oxidative stress injury, stabilized mitochondrial ultrastructure, inhibited cardiomyocyte apoptosis, and ultimately reduced myocardial infarct size. In aged myocardium, SpostC also played an excellent myocardial protective role.CONCLUSION: SpostC was able to upregulate HIF-1α expression, promote BNIP3-mediated mitochondrial autophagy, reduce myocardial infarct size, and alleviate myocardial I/R injury in aged mice.