七氟烷通过激活AMPK-ULK1通路介导的保护性自噬抑制LPS诱导的急性肺损伤

Abstract

Background Sevoflurane anesthesia is deemed as potential therapeutic drug for lipopolysaccharide (LPS)-induced acute lung injury (ALI), but the molecular mechanisms have not been fully delineated. Aim The present study explored the specific molecular mechanism of sevoflurane regulating autophagy to reduce LPS induced ALI . Methods Male C57BL/6J mice and mouse pulmonary microvascular endothelial cells (MPVECs) were treated with LPS to construct ALI models, and the levels of inflammation, apoptosis and autophagy were detected after treatment with sevoflurane. Meanwhile, cells were treated with autophagy inhibitor or AMP-activated protein kinase (AMPK)/unc-51 like autophagy activating kinase 1 (ULK1) pathway inhibitor in vitro to detect their effects on cell survival. Results Sevoflurane reduced inflammation, recovered cell division so as to suppress cell apoptosis and maintain cell survival, and activated autophagic flux in LPS-induced ALI models in vivo and in vitro . Of note, the suppressing effects of sevoflurane on LPS-induced cell death were abrogated by inhibiting autophagy. Moreover, we evidenced that sevoflurane promoted activation of the AMPK/ULK1 pathway in LPS-induced ALI models. Blockage of this pathway abrogated the promoting effects of sevoflurane on cell autophagy and cell viability in LPS-treated cells. Conclusion Collectively, sevoflurane suppresses apoptosis and inflammation via activating protective autophagy, thereby ameliorating LPS-induced ALI, and the AMPK/ULK1/ PIKFYVE pathway is responsible for the process.