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IR injury is a challenging pathophysiological process that is difficult to avoid clinically and frequently occurs during organ transplantation, surgery, shock resuscitation, and other processes. The major causes of IR injury include increased levels of free radicals, calcium overload, oxidative stress, and excessive inflammatory response. Ghrelin is a newly discovered brain\u2010intestinal peptide with anti\u2010inflammatory and antiapoptotic effects that improve blood supply. The role and mechanism of ghrelin in intestinal ischemia\u2013reperfusion (IIR) injury remain unclear. We hypothesized that ghrelin could attenuate IIR\u2010induced oxidative stress and apoptosis. To investigate this, we established IIR by using a non\u2010invasive arterial clip to clamp the root of the superior mesenteric artery (SMA) in mice. Ghrelin was injected intraperitoneally at a dose of 50\u2009\u03bcg\/kg 20\u2009min before IIR surgery, and [D\u2010Lys3]\u2010GHRP\u20106 was injected intraperitoneally at a dose of 12\u2009nmol\/kg 20\u2009min before ghrelin injection. We mimicked the IIR process with hypoxia\u2010reoxygenation (HR) in Caco\u20102 cells, which are similar to intestinal epithelial cells in structure and biochemistry. Our results showed that ghrelin inhibited IIR\/HR\u2010induced oxidative stress and apoptosis by activating GHSR\u20101\u03b1. Moreover, it was found that ghrelin activated the GHSR\u20101\u03b1\/Sirt1\/FOXO1 signaling pathway. We further inhibited Sirt1 and found that Sirt1 was critical for ghrelin\u2010mediated mitigation of IIR\/HR injury. Overall, our data suggest that pretreatment with ghrelin reduces oxidative stress and apoptosis to attenuate IIR\/HR injury by binding with GHSR\u20101\u03b1 to further activate Sirt1.<\/jats:p>","DOI":"10.1096\/fj.202302155rrr","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T12:00:31Z","timestamp":1717070431000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Ghrelin alleviates intestinal ischemia\u2013reperfusion injury by activating the\n                    <scp>GHSR<\/scp>\n                    \u20101\u03b1\/Sirt1\/\n                    <scp>FOXO1<\/scp>\n                    pathway"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5286-1433","authenticated-orcid":false,"given":"Shi\u2010shi","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Anesthesiology Renmin Hospital of Wuhan University  Wuhan 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