摘要
BACKGROUND Stress-related gastric mucosal damage or ulcer remains an unsolved issue for critically ill patients.Stress ulcer prophylaxis has been part of routine intensive care,but uncertainty and controversy still exist.Co-secreted with mucins,intestinal trefoil factor(ITF)is reported to promote restitution and regeneration of intestinal mucosal epithelium,although the mechanism remains unknown.AIM To elucidate the protective effects of ITF on gastric mucosa and explore the possible mechanisms.METHODS We used a rat model of gastric mucosal damage induced by water immersion restraint stress and lipopolysaccharide-treated human gastric epithelial cell line to investigate the potential effects of ITF on damaged gastric mucosa both in vivo and in vitro.RESULTS ITF promoted the proliferation and migration and inhibited necrosis of gastric mucosal epithelia in vitro.It also preserved the integrity of gastric mucosa by upregulating expressions of occludin and zonula occludens-1.In the rat model,pretreatment with ITF ameliorated the gastric mucosal epithelial damage and facilitated mucosal repair.The protective effects of ITF were confirmed to be exerted via activation of Akt signaling,and the specific inhibitor of Akt signaling LY249002 reversed the protective effects.CONCLUSION ITF might be a promising candidate for prevention and treatment of stressinduced gastric mucosal damage,and further studies should be undertaken to verify its clinical feasibility.
基金
Social Development Projects of Jiangsu Province,No.BE2017720
the National Natural Science Foundation of China,No.81701894
Jiangsu Provincial Medical Youth Talent,No.QNRC2016909 and No.QNRC2016908
Natural Science Foundation of Jiangsu Province,No.BK20190247
Science Foundation of Jiangsu Health Commission,No.H2018039
China Postdoctoral Science Foundation,No.2018M643890
Jiangsu Postdoctoral Science Foundation,No.2018K048A and No.2020Z193。
