[Effects of cyclooxygenase-2 on formation and healing of acetic acid-induced gastric ulcer in rats].

OBJECTIVE

To investigate the possible role of cyclooxygenase-2 (COX-2) inhibitor NS-398 in formation and healing of acetic acid-induced gastric ulcer in rats.

METHODS

Fourty eight male Sprague-Dawley rats weighed 160-180 g were perfused with acetic acid into the stomach to induce gastric ulcer and then divided into two groups. NS-398, a specific COX-2 antagonist, was injected subcutaneously 3 hours before and 21 hours after the perfusion with acetic acid and then injected every 24 hours with the dose of 6 mg.kg-1 to 24 rats (treatment group). The other 24 rats were injected subcutaneously with normal saline as controls. In both groups 8 rats were killed 1, 3, and 7 days after the induction of gastric ulcer by acetic acid respectively. RT-PCR and Western blotting were used to determine the expression of COX-2 mRNA and inducible nitric oxide synthase (iNOS) mRNA in the gastric mucosa at different time points. Prostaglandin E2(PGE2) concentration in gastric mucosa was determined by ELISA as a parameter reflecting the COX activity. The severity of ulcer was assessed by ulcer area.

RESULTS

COX-2 mRNA expression and PGE2 production were markedly increased in gastric mucosa after ulcer induction, especially in the basal part. After the treatment of NS-398, the increased PGE2 production was inhibited. The ulcer area in NS-398 group was significantly smaller than that in control group 1 day after ulcer induction with slighter congestion and edema around the ulcer. There was no significant difference in ulcer area between NS-398 treatment group and control group 3 days after ulcer induction. However, the ulcer area in NS-398 treatment group was significantly greater than that in control group 7 days after ulcer induction. Along with the severity changes of mucosal lesion, the iNOS expression and activity decreased markedly in the NS-398 group.

CONCLUSION

NS-398 inhibits COX-2 activity, thus alleviating inflammatory reaction in acetic acid induced gastric ulcer and averting further damage of tissues. However, it retards the ulcer healing by inhibiting PGE2 production in iNOS expression and activity in gastric mucosa.