Dexmedetomidine attenuates ferroptosis in OGD/R H9C2 cells through regulation of miR-326-5p/LCN2 axis

Abstract Myocardial ischemia-reperfusion injury (IRI) is a common complication in cardiac surgery. A series of cascade reactions occurs during IRI, including apoptosis, necrosis, autophagy and focal death. Ferroptosis, a new way of programmed death, has been found play key role in IRI. Alleviating ferroptosis may be a potential direction of IRI treatment. In this study, we found mir-326-5p was differently expressed in four myocardial injury-related GEO database. Importantly, it could affect cell activity and regulate ferroptosis in oxygen-glucose deprivation/reperfusion (OGD/R) H9C2 cells via acting on its target gene LCN2. Interestingly, besides ferroptosis, we also found that mir-326-5p/LCN2 axis had a synergistic effect on inflammatory response and autophagy in OGD/R H9C2. Notably, we identified dexmedetomidine (DEX) as a natural agonist of mir-326-5p. In general, DEX significantly increased the expression of mir-326-5p and decreased the expression of LCN2 in OGD/R H9C2 cells, clearing cellular Fe2+ and inhibiting ferroptosis.