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Effect of azathioprine upon inflammation in rats with ulcerative colitis induced by immune complex-combined TNBS/ethanol

Objective: To observe the therapeutic effects of azathioprine (AZA) on Immune Complex-Combined TNBS/Ethanol method induced ulcerative colitis (UC) in rats and to explore its possible mechanism.

Methods: 64 Wistar rats were divided into 2 groups. Normal control group (n=12) was injected with saline and model group (n=52) was set up by immune complex-combined TNBS/ethanol. 4 rats were sacrificed to observe the macroscopical focus of infection in bowels in 3 weeks and UC model was taken out. The UC model rats were randomly divided into model control group, AZA low, medium and high dose group 1, 2.5, 5 mg/kg, respectively. All model rats were daily injected (caudal vein) with corresponding drug for consecutive 4 weeks. During the 4-week treatment, disease activity index (DAI) were observed. At the end of treatment, morphological observation was carried out on rats' colon (colonic mucosal damage index (CMDI) scores and histological score (HS)); IL-6, IL-8, IL-17 and TNF-α were determined by ELISA and the expression of p-selectin in the colonic tissues was detected using immunohistochemistry (IHC).

Results: The DAI, CMDI and HS of the model group were significantly higher than that of the normal control group (all p<0.01), indicating successful establishment of UC model. The DAI, CMDI and HS of the group treated with AZA were lower than those of the model group (DAI, HS: p<0.05; CMDI: p<0.01). Immune Complex-Combined TNBS/Ethanol significantly elevated IL-6, IL-8, IL-17, TNF-α levels in serum as well as the p-selectin expression group in colon tissue compared with their control group (p<0.05). The low-dose AZA group, the medium-dose AZA group, and high-dose AZA group showed significant inhibition of elevation of serum IL-6IL-8IL-17TNF-α level and p-selectin expression in colon tissue.

Conclusions: AZA can alleviate intestinal inflammation and have a therapeutic effect for UC. Its mechanisms may be related to reduce the expression of proinflammatory cytokines and thus alleviate inflammatory response.

Author(s): Guodong Huang, Jing Xiong