{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T17:28:52Z","timestamp":1772386132981,"version":"3.50.1"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,9,10]],"date-time":"2015-09-10T00:00:00Z","timestamp":1441843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81200273"],"award-info":[{"award-number":["81200273"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2015,11]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Reflux esophagitis (RE<\/jats:styled-content>) is one of the common gastrointestinal diseases that are increasingly recognized as a significant health problem. This study was designed to investigate the role of p38 mitogen\u2010activated protein kinase (MAPK<\/jats:styled-content>) in experimental chronic RE<\/jats:styled-content> model of rats.<\/jats:p><\/jats:sec>Methods<\/jats:title>Chronic acid RE<\/jats:styled-content> rats were induced by fundus ligation and partial obstruction of the pylorus and treated with SB<\/jats:styled-content>203580 (a p38 MAPK<\/jats:styled-content> inhibitor, i.p., 1\u00a0mg\/kg\/day) for 14\u00a0days.<\/jats:p><\/jats:sec>Key Results<\/jats:title>Immunohistochemical staining and Western blotting results revealed the activation of p38 MAPK<\/jats:styled-content> signaling in the esophagus mucosa 14\u00a0days post injury. Through gross and histological assessment, we found that inhibition of p38 MAPK<\/jats:styled-content> activation by SB<\/jats:styled-content>203580 attenuated esophageal mucosal damage in RE<\/jats:styled-content> rats. Inhibition of p38 MAPK<\/jats:styled-content> activation in RE<\/jats:styled-content> rats attenuated esophageal barrier dysfunction, through enhancing the expression of tight junction proteins and reducing the expression of matrix matalloproteinases\u20103 and \u20109. Inhibition of p38 MAPK<\/jats:styled-content> activation in RE<\/jats:styled-content> rats reduced CD<\/jats:styled-content>68\u2010positive cells in esophagus mucosa and mRNA<\/jats:styled-content> levels of tumor necrosis factor (TNF)\u2010\u03b1<\/jats:italic>, interleukin (IL)\u20106, and IL<\/jats:styled-content>\u20101\u03b2<\/jats:italic> in esophagus and protein levels of TNF<\/jats:styled-content>\u2010\u03b1<\/jats:italic>, IL<\/jats:styled-content>\u20106, and IL<\/jats:styled-content>\u20101\u03b2<\/jats:italic> in serum. In addition, we found that inhibition of p38 MAPK<\/jats:styled-content> activation in RE<\/jats:styled-content> rats suppressed protein expression of inducible nitric oxide synthase and reduced formation of nitric oxide (NO<\/jats:styled-content>), 3\u2010nitrotyrosin, and malondialdehyde in esophagus.<\/jats:p><\/jats:sec>Conclusions & Inferences<\/jats:title>Inhibition of p38 MAPK<\/jats:styled-content> activation attenuated esophageal mucosal damage in acid RE<\/jats:styled-content> rats, possibly by modulating esophageal barrier function and regulating inflammatory cell\u00a0recruitment, and the subsequent formation of cytokines, NO<\/jats:styled-content>, and reactive oxygen species.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12664","type":"journal-article","created":{"date-parts":[[2015,9,10]],"date-time":"2015-09-10T14:48:35Z","timestamp":1441896515000},"page":"1648-1656","source":"Crossref","is-referenced-by-count":16,"title":["Inhibition of p38 MAPK<\/scp> activation 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