{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:54:23Z","timestamp":1780448063531,"version":"3.54.1"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T00:00:00Z","timestamp":1744675200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Myocardial ischemia\u2013reperfusion injury (MIRI) significantly affects the prognosis of cardiac surgery patients. The anesthetic dexmedetomidine (Dex) has shown protective effects against ischemia\u2013reperfusion injury in cardiomyocytes; however, its exact mechanism remains unclear. In this study, hypoxia\/reoxygenation (H\/R) and ischemia\/reperfusion (I\/R) models were used to investigate the effects of Dex on H9c2 cells and MIRI in mice. The roles of the Sirtuin 1\/Forkhead box O3a (Sirt1\/FoxO3a) pathway in the protective effects of Dex were explored using the Sirt1 inhibitor EX527 and FoxO3a gene silencing. Results showed that H\/R significantly reduced H9c2 cell viability, increased Lactate Dehydrogenase (LDH) leakage, and elevated reactive oxygen species (ROS) production. Dex pretreatment reversed these effects. Additionally, Dex significantly reduced the expression of Bcl\u20102\u2010associated X protein\/B\u2010cell lymphoma 2 (Bax\/Bcl\u20102), cleaved caspase\u20103, Beclin\u20101, and microtubule\u2010associated protein 1A\/1B\u2010light chain 3B (LC3B), inhibiting apoptosis and autophagy while increasing the expression of p62, Sirt1, and FoxO3a. The protective effects of Dex against H\/R injury were abolished by EX527 or FoxO3a silencing. In the mouse MIRI model, Dex pretreatment decreased serum LDH and Creatine Kinase\u2010MB (CK\u2010MB) levels, reduced myocardial infarct size and cardiac injury, and significantly improved left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS). These protective effects were markedly reversed by EX527. These findings indicate that Dex alleviates MIRI by restoring Sirt1 expression and activating FoxO3a.<\/jats:p>","DOI":"10.1111\/cbdd.70100","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T07:59:01Z","timestamp":1744703941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Role of the Sirt1\/Foxo3a Pathway in Mitigating Myocardial Ischemia\u2013Reperfusion Injury by Dexmedetomidine"],"prefix":"10.1111","volume":"105","author":[{"given":"Hanlin","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Renmin Hospital of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danyong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Affiliated Hospital of Guangdong Medical University  Zhanjiang Guangdong China"},{"name":"Shenzhen Institute of Research and 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