title: Rebamipide Promotes the Regeneration of Aspirin-Induced Small-Intestine Mucosal Injury through Accumulation of β-Catenin.
abstract: BACKGROUND
  The effect of rebamipide on repairing intestinal mucosal damage induced by nonsteroidal anti-inflammatory drugs and its mechanism remain unclear. In this study, we sought to explore the mechanism whereby rebamipide could promote the regeneration of aspirin-induced intestinal mucosal damage.
  
  
  METHODS
  BALB/c mice were administered aspirin (200 mg/kg/d) for 5 days to induce acute small intestinal injury (SII). Subsequently, SII mice were treated with rebamipide (320 mg/kg/d) for 5 days. The structure of intestinal barrier was observed with transmission electron microscope, and Zo-1 and occludin expressions were detected. The proliferative index was indicated by the percentage of proliferating cell nuclear antigen positive cells. The prostaglandin E2 (PGE2) levels in the small intestine tissues were measured by an enzyme immunoassay. The mRNA and protein expression levels of cyclooxygenase (COX) and β-catenin signal were detected in the small intestine using quantitative PCR and Western blot, respectively.
  
  
  RESULTS
  COX expression was significantly down-regulated in aspirin induced SII (P < 0.05). In SII mice treated with rebamipide, histopathological findings of aspirin-induced intestinal inflammation were significantly milder and tight junctions between intestinal epithelial cells were improved significantly. The proliferative index increased after rebamipide treatment when compared with that in the control mice. The expressions of COX-2, β-catenin, and c-myc and the PGE2 concentrations in small intestinal tissues were significantly increased in mice with rebamipide treatments (P < 0.05).
  
  
  CONCLUSIONS
  Rebamipide administration in aspirin-induced SII mice could improve the intestinal barrier structure and promote the regeneration of small intestinal epithelial injury through up-regulating COX-2 expression and the accumulation of β-catenin.
authors.affiliation: Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Wa
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Zhong-Sheng
authors.initials: ZS
authors.lastname: Xia
authors.affiliation: Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Jie-Yao
authors.initials: JY
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ouyang
authors.affiliation: Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Ti-Dong
authors.initials: TD
authors.lastname: Shan
authors.affiliation: Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 107 Yan Jiang Xi Road, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Qi-Kui
authors.initials: QK
authors.lastname: Chen
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D001241:Aspirin / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D007583:Jejunum / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010539:Permeability; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D015363:Quinolones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D012038:Regeneration / Q000187:drug effects*; D019108:Tight Junctions / Q000187:drug effects; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C495267:CTNNB1 protein, mouse; D008565:Membrane Proteins; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D015363:Quinolones; D012333:RNA, Messenger; D051176:beta Catenin; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone; C052785:rebamipide; D000409:Alanine; D001241:Aspirin