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Given the antioxidative effect of molecular hydrogen, some recent studies suggest the potential use of molecular hydrogen as a biomedicine for the treatment of ARDS. In this study, we aimed to explore the protective effects of magnesium hydride (MgH<jats:sub>2<\/jats:sub>) on two types of ARDS models and its underlying mechanism in a lipopolysaccharide (LPS)\u2010induced ARDS model of the A549 cell line. The results showed that LPS successfully induced oxidative stress, inflammatory reaction, apoptosis, and barrier breakdown in alveolar epithelial cells (AEC). MgH<jats:sub>2<\/jats:sub> can exert an anti\u2010inflammatory effect by down\u2010regulating the expressions of inflammatory cytokines (IL\u20101<jats:italic>\u03b2<\/jats:italic>, IL\u20106, and TNF\u2010<jats:italic>\u03b1<\/jats:italic>). In addition, MgH<jats:sub>2<\/jats:sub> decreased oxidative stress by eliminating intracellular ROS, inhibited apoptosis by regulating the expressions of cytochrome c, Bax, and Bcl\u20102, and suppressed barrier breakdown by up\u2010regulating the expression of ZO\u20101 and occludin. Mechanistically, the expressions of p\u2010AKT, p\u2010mTOR, p\u2010P65, NLRP3, and cleaved\u2010caspase\u20101 were decreased after MgH<jats:sub>2<\/jats:sub> treatment, indicating that AKT\/mTOR and NF\u2010<jats:italic>\u03ba<\/jats:italic>B\/NLRP3\/IL\u20101<jats:italic>\u03b2<\/jats:italic> pathways participated in the protective effects of MgH<jats:sub>2<\/jats:sub>. Furthermore, the in vivo study also demonstrated that MgH<jats:sub>2<\/jats:sub>\u2010treated mice had a better survival rate and weaker pathological damage. All these findings demonstrated that MgH<jats:sub>2<\/jats:sub> could exert an ARDS\u2010protective effect by regulating the AKT\/mTOR and NF\u2010<jats:italic>\u03ba<\/jats:italic>B\/NLRP3\/IL\u20101<jats:italic>\u03b2<\/jats:italic> pathways to suppress LPS\u2010induced inflammatory reaction, oxidative stress injury, apoptosis, and barrier breakdown, which may provide a potential strategy for the prevention and treatment of ARDS.<\/jats:p>","DOI":"10.1155\/2022\/5918954","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T23:35:14Z","timestamp":1651016114000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Magnesium Hydride Ameliorates Endotoxin\u2010Induced Acute Respiratory Distress Syndrome by Inhibiting Inflammation, Oxidative Stress, and Cell 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