Sevoflurane Postconditioning Regulates Mitophagy Through the PINK1/Parkin Pathway to Alleviate Myocardial Microcirculatory Reperfusion Injury

This study investigates whether sevoflurane postconditioning (SpostC) alleviates myocardial microcirculatory reperfusion injury by regulating Mitophagy via the PTEN-induced kinase 1 (PINK1)/Parkin pathway. A mouse model of myocardial ischemia/reperfusion (I/R) injury was established. Microvascular perfusion was assessed by immunofluorescence. Protein expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS), endothelin-1 (ET-1), PINK1, Parkin, microtubule-associated protein 1A/1B-light chain 3 (LC3)II/LC3I, and p62 was analyzed by Western blotting (WB). Hematoxylin-eosin and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to evaluate vascular pathology and infarct size. In vitro, human cardiac microvascular endothelial cells (hCMECs) were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R), with assessments of cell viability (cell counting kit-8), barrier function (FITC-dextran permeability and transendothelial electrical resistance), cytoskeletal integrity (immunofluorescence), and Mitophagy markers (WB). SpostC enhanced microvascular perfusion, reduced infarct size, suppressed excessive Mitophagy, and restored endothelial function. These protective effects were reversed by either the Mitophagy inducer carbonyl cyanide m-chlorophenylhydrazone (CCCP) or PINK1 overexpression. SpostC exerts protective effects on myocardial microcirculatory reperfusion injury by inhibiting the PINK1/Parkin-mediated Mitophagy pathway.

PINK1/Parkin; endothelial dysfunction; mitophagy; myocardial microcirculatory reperfusion injury; sevoflurane postconditioning.