Effect of Rebamipide on Acetic Acid-induced Gastric Ulcer in Rats: Involvement of Hepatocyte Growth Factor

Abstract

Background: Rebamipide is used clinically as an anti-ulcer agent, especially in Japan. The major mechanisms of rebamipide include prostaglandin induction and free radical scavenging. Since prostaglandins are inducers of hepatocyte growth factor (HGF), we examined the effect of rebamipide on the expression of HGF, c-met, cyclooxygenase-2 (Cox-2) and subtype of the prostaglandin E2 receptor (EP2) in acetic acid-induced gastric ulcer, a model of human ulcer. Methods: Ninety-six male Fisher rats were used in the experiments. Gastric ulcers were produced by injecting 50µl of 20% acetic acid into subserosa of the border between the fundic and antral gland areas. The rats of the rebamipide group were fed a diet containing 60 mg kg −1 day −1 rebamipide and killed on days 10, 30, 60, 90, 120 and 150 after ulceration. Reverse transcription polymerase chain reaction of HGF, c-met, Cox-2 and EP2 gene and immunohistochemistry of proliferating cell nuclear antigen (PCNA) were performed. Results: In the rebamipide group, gastric ulcer index was significantly smaller than in the control group at each time-point except at 10 days (P < 0.05, each); up-regulation of HGF, c-met, Cox-2 and EP2 mRNA was also observed. The mRNA level of HGF was significantly correlated with that of Cox-2 and EP2 (P < 0.05, each). The PCNA-labelled epithelial cells in the rebamipide group were also greater than in the control group on days 10, 30, 90 and 120 (P < 0.05, each). Conclusion: The study suggests that rebamipide has anti-ulcerative effects on gastric mucosal cells via up-regulation of HGF, c-met, Cox-2 and EP2.