Objective: To induce Crohn disease in rats by intraluminal instillations of different concentrations of 2,4,6-trinitrobenzenesulfonic acid (TNBS) and ethanol.
Methods: Crohn disease in rats was induced with enema containing TNBS and 50% ethanol with volume ratio of 2:1 (experimental group 1) or 1:1 (experimental group 2), or solution containing TNBS and anhydrous ethanol with volume ratio of 2:1 (experimental group 3) or 1:1 (experimental group 4). Equivalent volume of normal saline was used to set as the normal saline control, and rats without any treatment were set as the normal control group. The rats were killed at various time points (3, 7, 14 and 21 d) respectively. Colonic inflammation and damage were assessed microscopically and histologically.
Results: In the colon of rats in the experimental group 3, discontinuous erosion, ulceration and infiltration of neutrophils occurred after one week; pebble sign and even segmental inflammation appeared on day 14. On day 21, it appeared improvement in the colon tissue and obviously thickened bowel wall, but the inflammation was easily observed under the light microscope. Experimental group 1 was similar to experimental group 3 in appearance of the colon on days 3 and 7; on day 14, colonic inflammation and damage were improved as compared with the experimental group 3, but there were obvious individual differences in histological findings among rats in group 1. In the experimental group 2, the intestinal wall turned to be normal on day 14. In the experimental group 4, there were high mortality and extensive damage of colon tissues, and the pathological characteristics were quite different from Crohn disease in humans.
Conclusion: The characteristics of the rat model of Crohn disease induced with a enema containing TNBS and anhydrous ethanol with volume ratio of 2:1 are similar to the clinical features of human Crohn disease, including typical pathological characteristics and long duration of inflammation. It may be an ideal experimental model for studying pathogenesis of Crohn disease and for evaluating treatment effects.