Expression Of NF-κB,COX-2 And MCP-1 In Colon Tissue Of Mice With Colitis Induced By TNBS And Their Relationship

Objective To study the expression of nuclear factorκB(NF-κB),cyclooxygenase-2 (COX-2) and monocyte chemotactic protein-1 (MCP-1) in colon tissue of mice with colitis induced by TNBS and their relationship.Methods Totally sixty male SD rats were weighed ,numbered and equally randomized into two groups, one group use for normal control, and the other use for IBD model which induced by intrarectal administration of TNBS(125mg/kg in 50% ethacol). Two weeks later, taken whole colon tissue above anus, H.E staining, viewing histopatho- logical change of colon tissue with light microscope, immunohistochemical SABC staining and detect the lever of nuclear factor kappa B(NF-κB),cyclooxygenase-2 (COX-2) and monocyte chemotactic protein-1 (MCP-1) between normal control and IBD model, using computer image system detect integrate optical density of each index, and analysis the associativity of them. Analysis the associativity of mean optical density of each index between different extent of disease.Results IBD model, which induced by TNBS, is the mature model with ulcertion as the major appearance. The model emerge necrosis, ulcer, hyperblastosis, bowels be thick- ening, enteric cavity be shrinking after two weeks. H.E staining show that the tissue structure of normal control is common , but model appearance whole colon, full-thickness inflammation, necrosis, ulcer, crypt abscess, with a great quantity inflammatory cell infiltrate. The model were divide into Var. mitis(7 examples), medium-sized(19 examples), gravis type(4 examples). NF-κB was mainly express in nucleus;COX-2 and MCP-1 was mainly express in endochylema. The over expression level of NF-κB,Cox-2 and MCP-1 in colitis models respectively were significantly higher than the expression level of colitis tissues in nomal controls (P<0.01).The expression of COX-2 in protein was positively correlated with the NF-κBp65 (r=0.52, P<0.05), and the expression of MCP-1 in protein was also positively correlated with the NF-κBp65 (r=0.87, P<0.05). The expression of each one significantly correlated with diease severity(r=0.782,P <0.05; r=0.563,P <0.05; r=0.754,P <0.05). The expression of NF-κBp65 was significantly higher in pathologic medium-sized and gravis type than that in Var. mitis (39.7195±12.6728, 33.1449±10.6429 vs 22.4682±6.3794, P<0.05). The expression of COX-2 was significantly higher in pathologic medium-sized and gravis type than that in Var. mitis (10.0104±0.7518, 9.7280±1.1416 vs 8.3649±0.8104, P<0.01). The expression of MCP-1 was significantly higher in pathologic medium- sized and gravis type than that in Var. mitis (11.0002±1.0791,8.3498±1.9246vs 6.0419±1.3109, P <0.01).Conclusions The over expression level of NF-κB,Cox-2 and MCP-1 in colitis models respectively were significantly higher than the expression level of colitis tissues in nomal controls (P<0.01).The expression of COX-2 in protein was positively correlated with the NF-κBp65, and the expression of MCP-1 in protein was also positively correlated with the NF-κBp65. COX-2 and MCP-1 having NF-κB binding sites in their promoters. NF-κB possibly promote the expression of COX-2 and MCP-1 , but weather COX-2 and MCP-1 promote the expression of NF-κB need further study. The high expression of NF-κB,COX-2 and MCP-1 closely related in colitis. All of them played important role in the occurrence and development of colitis.