Salidroside inhibits the ferroptosis to alleviate lung ischemia reperfusion injury via the JAK2/STAT3 signalling pathway

Abstract

ObjectiveThe present study aims to investigate the protective potential of salidroside in both lung ischemia/reperfusion injury (LIRI) mice model and cell hypoxia/reoxygenation (H/R)model and the involvement of ferroptosis and JAK2/STAT3 pathway. Materials and methodsAfter we established the IR-induced lung injury model in mice, we administered salidroside and the ferroptosis inhibitor, ferrostatin-1, then assessed the lung tissue injury, ferroptosis (levels of reactive oxygen species level, malondialdehyde and glutathione), and inflammation in lung tissues. The levels of ferroptosis-related proteins (glutathione peroxidase 4, fibroblast-specific protein 1, solute carrier family 1 member 5 and glutaminase 2) in the lung tissue were measured with Western blotting. Next, BEAS-2B cells were used to establish an H/R cell model and treated with salidroside or ferrostatin-1 before the cell viability and the levels of lactate dehydrogenase (LDH), inflammatory factor, ferroptosis-related proteins were measured. The activation of the JAK2/STAT3 signaling pathway was measured with Western blotting, then its role was confirmed with STAT3 knockdown. ResultsRemarkably, salidroside was found to alleviate ferroptosis, inflammation, and lung injury in LIRI mice and the cell injury in H/R cell model. Severe ferroptosis were observed in LIRI mice models and H/R-induced BEAS-2B cells, which was alleviated by salidroside. Furthermore, salidroside could inhibit JAK2/STAT3 activation induced by LIRI. STAT3 knockdown could enhance the effect of salidroside treatment on H/R-induced cell damage and ferroptosis in vitro. ConclusionsSalidroside inhibits ferroptosis to alleviate lung ischemia reperfusion injury via the JAK2/STAT3 signaling pathway.