Dynamic progress of 2,4,6-trinitrobenzene sulfonic acid induced chronic colitis and fibrosis in rat model.

ABSTRACT

OBJECTIVE: To investigate the dynamic progress of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced chronic colitis and fibrosis in rat model. METHODS: In all, 44 Sprague-Dawley rats were randomly divided into the model and control groups. Colitis was induced by intrarectal injection of 10-30 mg TNBS in 50% ethanol enema weekly for 5 cycles. The control group received an equal volume of 50% ethanol. If the rat died during the procedure, necropsy was performed immediately. At the end of the 2nd, 3rd, 4th and 5th week the rats were sacrificed, and histological damage and fibrosis of the colon were examined using HE and Masson trichrome stain. The concentrations of Th1, Th2, Th17 cytokines in colon tissue were detected by ELISA, intestinal fibrosis-relevant cytokine expressions were detected by fluorescent quantification-polymerase chain reaction. RESULTS: Colitis model was successfully induced with a low mortality rate. The microscopic colonic damage score, collagen area, Th1/Th17 cytokines and expressions of intestinal fibrosis-relevant cytokines were significantly higher in the model group than those in the control group. Furthermore, the collagen area, content of interleukin 17 and expressions of intestinal fibrosis-related cytokines in the model group were more elevated in the chronic phase (after 3 to 4 cycles) than in the acute phase (P < 0.05). CONCLUSIONS: Multiple inflammatory responses participate in the formation and dynamic progression of TNBS-induced chronic colitis. In particular, acute colitis may turn into chronic colitis after 3 cycles of TNBS administration. This coincides with the formation of intestinal fibrosis which is concomitantly exacerbated after cycle 4.