{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:57:20Z","timestamp":1791190640786,"version":"4.1.0"},"reference-count":45,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology"],"abstract":"<jats:p>Introduction: Myocardial ischemia-reperfusion (I\/R) injury represents a key contributor to cardiac dysfunction and is associated with cardiomyocyte senescence. Dexmedetomidine (Dex) exhibits significant myocardial protective effects, but its molecular mechanisms in alleviating I\/R-induced cardiomyocyte senescence remain unclear. Methods: In this study, an I\/R injury model was established in C57BL\/6 mice. An in vitro injury model of H9C2 cardiomyocytes was constructed using the oxygen-glucose deprivation\/reoxygenation method to evaluate the effects of Dex on senescence in myocardial tissue and cardiomyocytes. Histopathological changes were assessed using hematoxylin and eosin and Masson staining, while cellular senescence was evaluated through senescence-associated \u03b2-galactosidase staining. The levels of myocardial infarction-related factors were detected by ELISA. The expression of senescence-related markers (p27, p21, and p16) was measured by qRT-PCR and WB, and apoptosis was measured by TUNEL assay. Cell viability, proliferation, and oxidative stress (OS) levels were assessed by CCK-8, EDU, and DCFH-DA probes. Results: In vivo and in vitro experiments showed that Dex alleviated I\/R-induced myocardial histopathological damage, improved cardiomyocyte viability and proliferation, reduced OS, and suppressed cellular senescence. Mechanistic studies revealed that Dex inhibited activation of the NF-\u03baB pathway by downregulating malate dehydrogenase 2 (MDH2), thereby attenuating cardiomyocyte senescence. Conclusion: Dex significantly mitigates I\/R injury-driving cardiomyocyte senescence by blocking the MDH2\/NF-\u03baB signaling, providing a potential therapeutic strategy for ischemic heart disease.<\/jats:p>","DOI":"10.1159\/pha\/aejag001","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T13:02:59Z","timestamp":1786021379000},"page":"1-1","source":"Crossref","is-referenced-by-count":0,"title":["Dexmedetomidine Alleviates Cardiomyocyte Senescence Induced by Ischemia-Reperfusion Injury via Inhibiting the MDH2\/NF-\u03baB 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