{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:48:54Z","timestamp":1791308934683,"version":"4.3.1"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Acute lung injury (ALI)\/acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality in the intensive care unit (ICU) and can cause excessive inflammation. Dexmedetomidine (DEX) is a drug that exerts anti\u2010inflammatory effects. Identifying the anti\u2010inflammatory mechanism of DEX in the context of ALI\/ARDS possesses potential significance for the prevention and treatment of ARDS. In this study, DEX was used to treat mouse models of cecal ligation and puncture (CLP) and lipopolysaccharide (LPS)\u2010stimulated cells. Immunofluorescence, western blot analysis, and flow cytometry were used to detect macrophage phenotypic markers in mice, and western blot analysis, real\u2010time qPCR (RT\u2010qPCR), ELISA, and immunofluorescence were used to detect macrophage phenotype markers in RAW264.7 cells. Flow cytometry was used to detect phenotypic markers of bone marrow\u2010derived macrophages (BMDM). Culture medium collected from macrophages was used to cultivate human non\u2010small cell adenocarcinoma epithelial cells (A549) to detect their aquaporins 1 (AQP1) expression and apoptosis status. Western blot analysis was used to detect the activation of the AMP\u2010activated protein kinase (AMPK)\/sirtuin 1(SIRT1) signaling pathway both in vivo and in vitro. The regulatory effect of DEX on macrophage phenotype remodeling was detected by knocking down AMPK expression in cells using AMPK shRNA. The results showed that in both in vivo and in vitro experiments, DEX downregulated the expression of M1 markers (tumor necrosis factor\u2010\u03b1 [TNF\u2010\u03b1], nitric oxide synthase [iNOS], and cluster of differentiation [CD]\u201086) and upregulated the expression of M2 markers (arginase\u20101 [ARG\u20101], interleukin [IL]\u201010, and CD206) in macrophages. The culture medium of macrophages treated with DEX alleviated the edema and apoptosis of A549 cells. DEX activates the AMPK\/SIRT1 signaling pathway in macrophages. After AMPK knockdown, the ability of DEX to regulate macrophage phenotype remodeling decreased. Together, this study suggests that DEX regulates macrophage phenotype remodeling by activating the AMPK\/SIRT1 pathway, thereby reducing ALI\/ARDS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbt.70108","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T08:30:13Z","timestamp":1734510613000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dexmedetomidine Regulates Macrophage Phenotype Remodeling Through AMPK\/SIRT1 to Alleviate Inflammatory Mediators and Lung Injury"],"prefix":"10.1002","volume":"39","author":[{"given":"Yi\u2010si","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing China"},{"name":"The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010kang","family":"Shi","sequence":"additional","affiliation":[{"name":"The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases The First Affiliated Hospital of Chongqing Medical University Chongqing China"},{"name":"Forensic Medicine and Biomedical Informatics Research Room Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke\u2010feng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Fengjie Hospital A Branch of The Second Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing China"},{"name":"The Chongqing Key Laboratory of Translational Medicine in Major Metabolic Diseases The First Affiliated Hospital of Chongqing Medical University Chongqing China"},{"name":"Department of Critical Care Medicine The First People's Hospital of Chongqing Liang Jiang New Area Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi\u2010hui","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xing","sequence":"additional","affiliation":[{"name":"Forensic Medicine and Biomedical Informatics Research Room Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8201-1595","authenticated-orcid":false,"given":"Fang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0069-0"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201211-1981OC"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-018-2079-9"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(20)30404-5"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2020.06.009"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202005-1885OC"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03148-w"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-020-01378-2"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00547-x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.110678"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2023.115331"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115080"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2021.2000723"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12061206"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-06296-9"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000086896.90343.13"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-018-0211-9"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011802"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(14)70097-9"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201701-0107CP"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psychres.2023.115172"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.18611"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.9955"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.101954"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/10641963.2022.2093893"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-022-01117-5"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.03.009"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.08.010"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2022.108176"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2021.108875"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.04.022"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103412"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00525.2007"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26429"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13105-017-0563-3"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00300.2011"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/10641963.2023.2205049"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2021.01.009"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.49426"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2022.110363"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.45862"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-018-0878-0"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T08:02:14Z","timestamp":1746172934000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,18]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1002\/jbt.70108"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70108","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,18]]},"assertion":[{"value":"2024-06-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70108"}}