Prevention and treatment effects of celecoxib via coloclysis in mice with ulcerative colitis associated intestinal mucosa dysplasia

Objective To compare the prevention and treatment effects of different concentrations of celecoxib via coloclysis in mice with ulcerative colitis associated intestinal mucosa dysplasia and analyze the possible mechanism. Methods Sixty C57BL/6 male mice were randomly divided into six groups(n=10): the high(A), middle(B), low(C)doses of celecoxib groups, mesalazine group(D), model group(E), blank group(F).Azoxymethane / Dextran sulfate sodium(AOM/DSS)combined technique was used to establish the experimental mouse mode.After modeling for five days, the mice were treated accordingly: mice in experimental group A, B, C were given the high, medium and low doses of celecoxib(1.5 mg/mL, 1.0 mg/mL, 0.5 mg/mL)via coloclysis, mice in group D were given mesalazine via coloclysis, mice in group E were given the same dose of 0.9% sodium chloride injection via coloclysis.The mice were sacrificed at day 23 after treatment, the changes of colon tissue were observed with naked eyes, and the differences of colon pathological changes and expression of immunohistochemistry COX-2, CDX-2, BCL-2 were assayed under microscope.Meanwhile, the levels of serum cytokines were detected by Elisa. Results Visually, compared with group E, the colon surface of group A and B were smoother and the vascular texture were clearer.In group C and D, the colon surface was less smooth, while the stool was relatively forming.HE staining showed that there were more complete mucosa, neater glands in group A and B.However, the major types of group C was superficial ulcer, group D was causally with lymphocyte infiltration, group E was mainly chronic inflammation associated with light to moderate hyperplasia.The serum inflammatory cytokines IL-6, TNF-α content of each treatment group declined significantly(P＜0.05), the result of immunohistochemical detection showed that COX-2 scores of group A and B were significantly lower than group C, D, E, BCL-2 scores of group A, B, D were significantly lower than group C, E, CDX-2 scores of group A, B, C, D was significantly higher than group E(P＜0.05). Conclusion Celecoxib via coloclysis has the effect on prevention and treatment of ulcerative colitis associated intestinal mucosa dysplasia and the effect of middle and high dose is obvious, meanwhile, the mechanism may be related with a down-regulation in the expression of COX-2, BCL-2, and the reductionof production of inflammatory factors IL-6, TNF-α.