Therapeutic Effect Of Kuijiekang In Rats With TNBS-induced Crohn’s Disease

Objective: This reaserch aim was to study the effects of Kuijiekang by different doses on Crohn’s disease model induced by TNBS through administration of enema and gavage routes. By observing rat eating, fur color, activity, body weight and growth; stool; colon specimens; intestinal mucosal injury and repair, etc., we determined the optimal concentration of modeling and choiced modeling conditions, so as to provide experimental evidence for the treatment of disease in clinic.Methods: 1. Depending on the concentration of TNBS established rat model of Crohn. The 10 rats were randomly divided into low dose TNBS model group(n=4), TNBS middle dose model group(n=4), TNBS high dose model group(n=4) and normal group(n=2), half male and half female. The general situation was observed, including rat eating, body weight, stool, fur color, activity and mental state, situation stool(fecal occult blood, bloody stools, diarrhea). Two weeks later the mice were sacrificed, and then take the colon tissue, colon tissue damage in rats, confirming the formation of Crohn’s disease. 2. Grouping: 72 rats were randomly divided into 12 groups. Normal control group, model group, Kuijiekang high dose group, middle dose group, low dose group, positive control group(n = 6), half male and half female. 3. Medical treatement: After modeling 24 h different dose Kuijiekang were administrated once daily for 21 days. The observation continued until 24 h after the last administration. 4. Efficacy evaluation. Observe the general situation, including rat eating, body weight, stool, fur color, activity and mental state; situation stool(fecal occult blood, bloody stools, diarrhea), in disease activity index(disease activity index, DAI) score every day. After the end of the experiment the results recorded including Kuijiekang enema administration or oral administration on rat serum interferon-γ(IFN-γ), intestinal mucosa glutamine(Gln), interleukin-l(IL-1), interleukin-4(IL-4), and interleukin-10(IL-10) influence and the effect of drugs on colon tissue injuries of scores and pathology.Results: 1. TNBS-induced model of Crohn’s disease can cause weight loss in rats, to the naked eye or bloody stools positive for fecal occult blood, DAI score higher. After modeling experiments confirmed TNBS enema can induce the formation of Crohn’s disease. After with low modeling dose of 100mg/kg(3m L/kg), four days after the symptoms tend to improve at 6-8 days after the stool has basically taken shape, visual observation and no mucus bloody stool. Two weeks later, when dissected colon has gradually heal itself. And after with middle modeling dose of 125mg/kg(3.75 m L/kg), there has no death case in rats, and no self healing occurred after two weeks. But after with high modeling dose of 150mg/kg(4.5m L/kg), high mortality in rats. So choose modeling concentration 125mg/kg of TNBS-induced model of Crohn’s disease. 2. Different doses of Kuijiekang, enema or oral administration can improve DAI rates and increased TNBS induced lower serum IFN-γ, IL-1 levels, increased mucosal Gln, remission of Crohn’s disease and histological changes, including in particular in high dose of Kuijiekang enema administration was more effective. 3. The therapeutic effect of Kuijiekang enema administered is better than oral administration.Conclusion: In this study, the effects of different concentrations of TNBS induced rat model of Crohn’s disease, confirmed TNBS enema modeling can induce the formation of Crohn’s disease, and to determine the optimal concentration of modeling and to choice modeling conditions, the experimental basis for further study. Kuijiekang enema or oral administration can alleviate the TNBS induced model of Crohn’s disease. This therapeutic effect is more obviously in Kuijiekang enema administered in high dose group.