[Mechanism of exacerbation of colonic damage in experimental colitis treated with celecoxib].
摘要
OBJECTIVE: To assess the mechanism of exacerbation of colonic damage in rat colitis model induced by trinitrobenzene sulfonic acid (TNBS) treated with celecoxib (a selective COX-2 inhibitor). METHODS: The rats were randomized into four groups. Group 1 and Group 2 were study groups. Group 3 and Group 4 were control groups. Colitis was induced by intracolonic administration of TNBS (25 g/L) in a vehicle of 50% ethanol (0.25 mL) of study groups. The rats of study groups were treated orally, beginning 3 h before induction of colitis and continuing twice per day thereafter for up to 7 d, with celecoxib (1.25 mg/kg, Group 1) and distilled water (1 mL/0.3 kg, Group 2) respectively. In control experiments, the rats of Group 4 were treated orally with celecoxib (1.25 mg/kg) twice per day for up to 7 d. Group 3 rats were healthy control rats. All the rats that survived until the end of the experiment (d 7) were killed and the severity of colonic inflammation was assessed. The COX-2 protein expression in colon tissues was examined by immunohistochemistry. RESULTS: The colonic damage of Group 1 was exacerbated as compared with Group 2. The inflammatory index of colon tissues of Group 1 (8.5+/-2.5) was significantly reduced, as compared with Group 2 (13.5+/-1.9, P<0.05). The levels of COX-2 protein expression was decreased significantly in Group 1 (3.7 x 10(-2)+/-9.5 x 10(-3)) as compared with Group 2 (11.4 x 10(-2)+/-3.8 x 10(-2), P<0.05). The positive rate of COX-2 expression in neural cells of the myenteric plexus in Group 1 (30%) was decreased as compared with Group 2 (90%, P<0.05). No difference was found in the inflammatory index, the levels of COX-2 protein expression and the positive rate of COX-2 expression in neural cells of the myenteric plexus of Group 3 and Group 4. CONCLUSION: Selective COX-2 inhibitor-celecoxib could decrease the expression of COX-2 in intestinal tissue, attenuate the inflammatory index of colon tissues of experimental colitis induced by TNBS. But