2003•Zhongguo yaolixue tongbaoRequires access
Induction of cyclooxygenase-2 in rat gastric mucosa by rebamipide
Wei Sun
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Abstract
AIM Recent studies indica te an expression of mitogen-inducible cyclooxygenase (COX-2) in gastric mucosa. Rebamipide, a mucoprotective agent, has been reported to prevent various acute experimental gastric mucosal lesions and to accelerate the healing of chronic ulcers. However, the precise mechanisms of gastroprotection are unclear. Therefore, the present study was designed to clarify the relationship between protective effects of rebamipide and COX-2 expression in rat gastric mucosa. METHODS Male sprague-dawley rats were given 5, 15 and 50 mg·kg -1 ·d -1 of rebamipide for two weeks. The expression of COX-1 and COX-2 in gastric mucosa was determined by western blot analysis and immunohistochemical staining. The level of PGE 2 in gastric mucosa was measured by enzyme immune assay. The protective action of rebamipide against gastric injury caused by 0 6 mol·L -1 HCl was investigated. Effects of a specific COX-2 inhibitor NS-398 on the PGE 2 synthesis in gastric mucosa and the mucosal protection afforded by rebamipide were evaluated. RESULTS COX-2 expression was enhanced, while COX-1 expression did not change significantly in stomach after treatment with rebamipide. The gastric mucosal PGE 2 levels were (2293±373), (3400±493) and (3933±667) pg·g -1 wet wt in the groups treated with 5,15,or 50 mg·kg -1 of rebamipide respectively, which were significantly higher than that in the control group (1467±400) pg·g -1 wet wt (P0 05). The lesion index induced by HCl were (2 11±0 61)%, (1 42±0 41)%, (1 04±0 23)% respectively in the rebamipide groups and (3 63±0 96)% in the control group (P0 05). A specific COX-2 inhibitor blocked the rebamipide-induced increase in mucosal PGE 2, and mucosal protection induced by rebamipide. CONCLUSION This study demonstrates that rebamipide induces COX-2 expression, increases PGE 2 level, and enhances gastric mucosal defense in a COX-2 dependent manner. Thus, COX-2 plays an important role in the effects of rebamipide on gastric mucosal protection.