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This paper examined the protective effect of DEX in LIRI and elucidated the potential regulation involved. LIRI was induced in mice, followed by the detection of pulmonary arterial pressure, lung compliance, pathological changes, pulmonary vascular permeability, oxidative stress, inflammation, and apoptosis. Mice were infected with overexpression (OE)\u2010mitogen\u2010activated protein kinase kinase kinase 8 (MAP3K8) adenovirus and treated with DEX. MAP3K8 expression was examined in mouse lung tissue and pulmonary microvascular endothelial cells (PMVECs). Cells were infected using OE\u2010MAP3K8 lentivirus and treated with DEX, followed by detection of cell viability and apoptosis, VE\u2010cadherin and \u03b1\u2010E\u2010catenin, and pro\u2010inflammatory factors. Rescue experiments were performed by MAP3K8 overexpression and combined extracellular signal\u2010regulated protein kinase (ERK) pathway blocker, PD98059. The results demonstrated that DEX protected mice from LIRI. DEX inhibited MAP3K8 expression. MAP3K8 overexpression increased ERK1\/2 phosphorylation and activated the ERK pathway. Upregulation of MAP3K8 impaired the protective effect of DEX in\u00a0vivo and in\u00a0vitro, which was reversed by the ERK inhibitor PD98059. Overall, DEX achieved its protective effect against LIRI by inhibiting the MAP3K8\u2010ERK axis.<\/jats:p>","DOI":"10.1002\/kjm2.70045","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T09:41:38Z","timestamp":1747302098000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dexmedetomidine Blocks the <scp>ERK<\/scp> Pathway by Inhibiting <scp>MAP3K8<\/scp> to Achieve a Protective Effect in Lung Ischemia\/Reperfusion Injury"],"prefix":"10.1002","volume":"41","author":[{"given":"Chun\u2010Huan","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology The Second Affiliated Hospital of Mudanjiang Medical University  Mudanjiang Heilongjiang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Critical Medicine The Second Affiliated 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