The Effects And Mechanisms Of Infliximab On Rat Colitis Induced By Trinitrobenzene Sulfonic Acid

ObjectiveTo Investigated the Infliximab therapeutic action on rat colitis caused by trinitrobenzene sulfonic acid (TNBS), and research its interaction mechanisms, to provide certain experimental evidence on clinical treatment of ulcerative colitis.MethodsTwenty healthy male Wistar rats were divided randomly into normal control group and model group, ten in each group. Model group makes use of 5% Trinitrobenzene sulfonic acid (TNBS)/ anhydrous ethanol solution (100mg/kg/piece) to enema induced rat colitis model, the normal model uses isovolumic normal saline to enema. From the 7th day after modeling, both of the 2 groups should be given 0.9% Sodium chloride solution to Gastric lavage, once a day, 14 days altogether. On the 21st day, execute all the rats and take specimen. To rate the rats'disease activity index, colitics common morphous damage index, tissue damage index in order to judge whether the modeling is successful. Based on this experiment, forty healthy male Wistar rats were divided randomly into normal control group, model group, prednisone group and infliximab group- each group of ten. Except normal control group, make colitis model on the other 3 groups. From the 7th day, provide Infliximab 30mg/kg to infliximab group. On the 7th and 14th day, Infliximab was given only once separately Intraperitoneal injection; prednisone group was given prednisone 6mg/kg, normal control group and model group were given 0.9% Sodium chloride solution separately, and which were gastric lavage once a day for 14 days. On the 21st day, execute all the rats and take specimen. Besides mark the above mentioned indexes, we also detect the content of tumor necrosis factor-α(TNF-α)and Interleukin-10(IL-10) in peripheral blood serum, colonic mucosa and milt spleen through enzyme-linked immunosorbent assay(ELISA).ResultsContrast with model group, there is substantial reduction on mark of disease activity index, colitics common morphous damage index, tissue damage index on normal control group, there is statistical significance of the difference(P<0.01). It means that enema through trinitrobenzene sulfonic acid can induce rat colitis successfully. For infliximab group, there is substantial reduction on mark of common morphous damage index in comparison with model group(P<0.01), the other 2 types mark are also reduced(P<0.05); Compare prednisone group with model group, mark of common morphous damage index was reduced substantially(P<0.01),but the other 2 types reduction were not substantial(P>0.05). It demonstrates that there is better efficacy of Infliximab. In contrast with normal control group, model group is significant increase of TNF-αcontent in peripheral blood serum, colonic mucosa and milt spleen, there is statistical significance of the difference(P<0.01); Compare with model group, there is significant reduction of the 3 types of tissue in infliximab group, there is statistical significance of the difference(P<0.01);Compare prednisone group with model group, besides there is significant reduction of the content of TNF-αin peripheral blood serum(P<0.01), there is no obvious reduction of the other 2 types(P>0.05). In contrast with normal control group, model group is substantial reduction of IL-10 content in peripheral blood serum and colonic mucosa, there is statistical significance of the difference(P<0.01); compare with model group, content of IL-10 in peripheral blood serum and colonic mucosa of infliximab group increased significantly(P<0.01);Compare prednisone group with model group, content of IL-10 in colonic mucosa increased(P<0.05), but there is no increasing in peripheral blood serum(P>0.05).There is no statistical significance of the difference of IL-10 content of each group in milt spleen(P>0.05).It demonstrate that Infliximab can reduce the TNF-αcontent in tissues, increase content of IL-10, thus can control the development of inflammation, which has better effect than prednisone for ulcerative colitis of rats.ConclusionsProvide 5% trinitrobenzene sulfonic acid/ anhydrous ethanol solution (100mg/kg/piece) disposable enema to Wistar rats can induce experimental colitis model. Infliximab can increase IL-10 content by reducing TNF-αcontent in tissue, consequently control development of inflammation, lysis clinical symptoms of rats with colitis, and can provide certain experimental evidence for clinical treatment of Ulcerative colitis.