Effect Of Selective COX-2 Inhibitor (Celecoxib) On Rat IBD Inflamation Repairation

Objects: An investigation was conducted to assess the effects and mechanism of celecoxib[a selective cyclooxygenase(cox)-2 inhibitor]on a rat colitis model induced by trinitrobenzene sulfonic acid(TNBS). Methods: The rats were divided into seven grous. Group 1, 2, 3, 4, 5 were experimental groups. Group 6, 7 were control groups. Colitis was induced by intracolonic administration of TNBS in rats of experiment grous. Three hours before induction of colitis, the rats were beginning and continuing to treat orally with celecoxib(group 1 to 4) in different dose and distilled water(group 5)twice per day for 7 days, respectively. Group 6 served as healthy control. Group 7 served as celecoxib control and the rats treated orally with celecoxib twice per day for 7 days. All rats that survived until the end of the experiment(7 d)were killed. The mortality and the severity of damage were assessed. The prostaglandin E₂(PGE₂) concentrations of colonic mucosa were tested by ELISA and Nuclear factor-κB was tested by RT-PCR. Results: There's correlation between celecoxib dose and the mortality of celecoxib experiment groups(group 1 to 4). The colonic damage scores in experiment groups were significantly higher than that of healthy control group(P＜0.01). H test shows great difference was found between celecoxib experiment groups(group1, 2, 3, 4)(P＜0.05). No difference was found in scores between group 6 and group 7(P＞0.05). Great difference was found between experiment group and control group; The PGE₂ concentrations of experiment groups(group 1 to 5) were significantly higher than that of group 6 (P＜0.01). Great difference was found between experiment groups(P＜0.05), highly correlation was found between PGE₂ descension and celecoxib dose, PGE₂ expression was restrained under celecoxib treament. No difference was found in PGE₂ concentration in control groups (group 6 and group 7)(P＞0.05); NF-κB RT-PCR shows reverse effect compared with PGE₂ expression under celecoxib treatment, NF-κB was activated by celecoxib, but no correlation between NF-κB expression and celecoxib dose.Conclusions: These results suggest that treatment with celecoxib(selective COX-2 inhibitor)resulted in exacerbation of inflammation-associated colonic injury in experimental colitis induced by TNBS. ELISA and RT-PCR show that celecoxib promoted NF-κB expression and declined PGE₂ level. The preliminary study shows that the mechanism is related to the suppression caused by COX-2 inhibitor for the PGs derived from COX-2, but further study is still needed for identifying if there are some other related reasons.