{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:25:41Z","timestamp":1790717141985,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Myocardial ischemia\u2013reperfusion injury (MIRI) causes severe clinical complications in patients. Although gemfibrozil (GEM) has been extensively studied in metabolic diseases, its effects on MIRI remain unknown. In this study, we investigated the pharmacological effects and molecular mechanisms of GEM in alleviating MIRI through adenosine 5\u2032\u2010monophosphate\u2010activated protein kinase (AMPK) modulation. The results showed that pre\u2010administration of GEM (100\u2009mg\/kg) provided significant protection against MIRI in mice, as indicated by reduced infarct size, lower cardiac injury markers such as hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ), lactate dehydrogenase (LDH), and creatine kinase (CK), and improved cardiac function. This cardioprotective effect of GEM was associated with enhanced myocardial antioxidant capacity, as shown by decreased dihydroethidium (DHE) fluorescence density and reduced nitric oxide (NO) and malondialdehyde (MDA) levels in ischemic cardiac tissue. GEM pretreatment also prevented the I\/R\u2010induced increase in TUNEL\u2010positive cells and expression of caspase\u20103, caspase\u20109, and Bax, as well as the I\/R\u2010induced decrease in Bcl\u20102 expression in ischemic cardiac tissue, indicating an anti\u2010apoptotic effect of GEM in MIRI. In addition, GEM pretreatment prevented the I\/R\u2010induced increase in mRNA expression levels of tumour necrosis factor\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    (\n                    <jats:italic>Tnf\u2010\u03b1<\/jats:italic>\n                    ), interleukin\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    (\n                    <jats:italic>Il\u20101\u03b2<\/jats:italic>\n                    ), and\n                    <jats:italic>Il\u20106<\/jats:italic>\n                    in ischemic cardiac tissue. Further analysis showed that GEM administration prevented the I\/R\u2010induced decrease in phospho\u2010AMPK levels in ischemic cardiac tissue, and pharmacological inhibition of AMPK with dorsomorphin (DSMF) abolished all cardioprotective effects of GEM. Taken together, these results suggest that GEM mitigates MIRI\u2010induced cardiac injury by inhibiting apoptosis and oxidative stress via modulation of AMPK, supporting its potential for reducing MIRI\u2010related cardiac damage.\n                  <\/jats:p>","DOI":"10.1111\/1440-1681.70106","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T03:36:21Z","timestamp":1771385781000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gemfibrozil Prevents Myocardial Ischemia\u2013Reperfusion Injury in Mice Through\n                    <scp>AMPK<\/scp>\n                    Activation"],"prefix":"10.1111","volume":"53","author":[{"given":"Yilong","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery Affiliated Hospital of Nantong University  Nantong China"},{"name":"Department of Pharmacology, School of Pharmacy Nantong University  Nantong 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