Additive Effects of Rebamipide Plus Proton Pump Inhibitors on the Expression of Tight Junction Proteins in a Rat Model of Gastro-Esophageal Reflux Disease
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: The aim of this study was to investigate the effects of rebamipide on tight junction proteins in the esophageal mucosa in a rat model of gastroesophageal reflux disease (GERD). Methods: GERD was created in rats by tying the proximal stomach. The rats were divided into a control group, a proton pump inhibitor (PPI) group, and a PPI plus rebamipide (PPI+R) group. Pantoprazole (5 mg/kg) was administered intraperitoneally to the PPI and PPI+R groups. An additional dose of rebamipide (100 mg/kg) was administered orally to the PPI+R group. Mucosal erosions, epithelial thickness, and leukocyte infiltration into the esophageal mucosa were measured in isolated esophagi 14 days after the procedure. A Western blot analysis was conducted to measure the expression of claudin-1, -3, and -4. Results: The mean surface area of mucosal erosions, epithelial thickness, and leukocyte infiltration were lower in the PPI group and the PPI+R group than in the control group. Western blot analysis revealed that the expression of claudin-3 and -4 was significantly higher in the PPI+R group than in the control group. Conclusions: Rebamipide may exert an additive effect in combination with PPI to modify the tight junction proteins of the esophageal mucosa in a rat model of GERD. This treatment might be associated with the relief of GERD symptoms.
Abstract
Background/Aims: The aim of this study was to investigate the effects of rebamipide on tight junction proteins in the esophageal mucosa in a rat model of gastroesophageal reflux disease (GERD). Methods: GERD was created in rats by tying the proximal stomach. The rats were divided into a control group, a proton pump inhibitor (PPI) group, and a PPI plus rebamipide (PPI+R) group. Pantoprazole (5 mg/kg) was administered intraperitoneally to the PPI and PPI+R groups. An additional dose of rebamipide (100 mg/kg) was administered orally to the PPI+R group. Mucosal erosions, epithelial thickness, and leukocyte infiltration into the esophageal mucosa were measured in isolated esophagi 14 days after the procedure. A Western blot analysis was conducted to measure the expression of claudin-1, -3, and -4. Results: The mean surface area of mucosal erosions, epithelial thickness, and leukocyte infiltration were lower in the PPI group and the PPI+R group than in the control group. Western blot analysis revealed that the expression of claudin-3 and -4 was significantly higher in the PPI+R group than in the control group. Conclusions: Rebamipide may exert an additive effect in combination with PPI to modify the tight junction proteins of the esophageal mucosa in a rat model of GERD. This treatment might be associated with the relief of GERD symptoms.
참고문헌 (19)
- Vakil N, "The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus", Am J Gastroenterol, 101, pp.1900~1920 (2006)[DOI]
- Farre R, "Short exposure of oesophageal mucosa to bile acids, both in acidic and weakly acidic conditions, can impair mucosal integrity and provoke dilated intercellular spaces", Gut, 57, pp.1366~1374 (2008)[DOI]
- van Malenstein H, "Esophageal dilated intercellular spaces (DIS) and nonerosive reflux disease", Am J Gastroenterol, 103, pp.1021~1028 (2008)[DOI]
- Caviglia R, "Dilated intercellular spaces of esophageal epithelium in nonerosive reflux disease patients with physiological esophageal acid exposure", Am J Gastroenterol, 100, pp.543~548 (2005)[DOI]
- Tobey NA, "Dilated intercellular spaces: a morphological feature of acid reflux--damaged human esophageal epithelium", Gastroenterology, 111, pp.1200~1205 (1996)[DOI]
- Genta RM, "Review article: the role of rebamipide in the management of inflammatory disease of the gastrointestinal tract", Aliment Pharmacol Ther, 18(Suppl 1), pp.8~13 (2003)[DOI]
- Yoshida N, "Management of recurrence of symptoms of gastroesophageal reflux disease: synergistic effect of rebamipide with 15 mg lansoprazole", Dig Dis Sci, 55, pp.3393~3398 (2010)[DOI]
- Gunzel D, "Claudins and the modulation of tight junction permeability", Physiol Rev, 93, pp.525~569 (2013)[DOI]
- Asaoka D, "Altered localization and expression of tight-junction proteins in a rat model with chronic acid reflux esophagitis", J Gastroenterol, 40, pp.781~790 (2005)[DOI]
- Oguro M, "Dissociation and dispersion of claudin-3 from the tight junction could be one of the most sensitive indicators of reflux esophagitis in a rat model of the disease", J Gastroenterol, 46, pp.629~638 (2011)[DOI]
- Katada K, "Prevention by rebamipide of acute reflux esophagitis in rats", Dig Dis Sci, 50(Suppl 1), pp.S97~S103 (2005)[DOI]
- Matysiak-Budnik T, "Positive effect of rebamipide on gastric permeability in mice after eradication of Helicobacter felis", Scand J Gastroenterol, 35, pp.470~475 (2000)[DOI]
- Matysiak-Budnik T, "Alterations of epithelial permeability by Helicobacter and IL-1beta in vitro: protective effect of rebamipide", Dig Dis Sci, 46, pp.1558~1566 (2001)[DOI]
- Miwa H, "Rikkunshito, a traditional Japanese medicine, may relieve abdominal symptoms in rats with experimental esophagitis by improving the barrier function of epithelial cells in esophageal mucosa", J Gastroenterol, 45, pp.478~487 (2010)[DOI]
- Bjorkman EV, "Esophageal barrier function and tight junction expression in healthy subjects and patients with gastroesophageal reflux disease: functionality of esophageal mucosa exposed to bile salt and trypsin in vitro", Scand J Gastroenterol, 48, pp.1118~1126 (2013)[DOI]
- Xu XB, "Expression of claudin-3 in the esophagus and larynx of rat reflux model", Auris Nasus Larynx, 41, pp.539~542 (2014)[DOI]
- Arakawa T, "Rebamipide, novel prostaglandin-inducer accelerates healing and reduces relapse of acetic acid-induced rat gastric ulcer. Comparison with cimetidine", Dig Dis Sci, 40, pp.2469~2472 (1995)[DOI]
- Shin WG, "Can rebamipide and proton pump inhibitor combination therapy promote the healing of endoscopic submucosal dissection-induced ulcers? A randomized, prospective, multicenter study", Gastrointest Endosc, 75, pp.739~747 (2012)[DOI]
- Yoshida N, "Rebamipide protects against activation of neutrophils by Helicobacter pylori", Dig Dis Sci, 41, pp.1139~1144 (1996)[DOI]
