Mitochondrial autophagy is involved in myocardial protection of
sevoflurane postconditioning (SPostC) and in diabetic state this protective effect is weakened due to impaired HIF-1 signaling pathway. Previous studies have proved that
deferoxamine (DFO) could activate impaired HIF-1α in diabetic state to restore the cardioprotective of
sevoflurane, while the specific mechanism is unclear. This study aims to investigate whether HIF-1/BNIP3-mediated mitochondrial autophagy is involved in the restoration of
sevoflurane postconditioning cardioprotection in diabetic state.
Ischemia/reperfusion (I/R) model was established by ligating the anterior descending coronary artery and
sevoflurane was administered at the first 15 min of reperfusion.
Myocardial infarct size, mitochondrial ultrastructure and autophagosome,
ATP content, mitochondrial membrane potential, ROS production, HIF-1α, BNIP3, LC3B-II,
Beclin-1, P62,
LAMP2 protein expression were detected 2 h after reperfusion, and cardiac function was evaluated by ultrasound at 24 h after reperfusion. Our results showed that with DFO treatment, SPostC up-regulated the expression of HIF-1α and BNIP3, thus reduced the expression of key autophagy
proteins LC3B-II,
Beclin-1, p62, and increased the expression of LAMP2. Furthermore, it reduced the accumulation of autophagosomes and ROS production, increased the content of
ATP, and stabilized the membrane potential. Finally, the
myocardial infarction size was reduced and cardiac function was improved. Taken together, DFO treatment combined with SPostC could alleviate
myocardial ischemia reperfusion injury in diabetic rats by restoring and promoting HIF-1/BNIP3-mediated mitochondrial autophagy.