Effect Of Taurine On Colonic Fibrosis In Rats With Colitis Induced By 2,4,6-trinitrobenzene Sulphonic Acid

Background:The incidence of Crohn's disease(CD) is increasing in China. Intestinal fibrostenosis, a common complication of CD with incidence of over one third, is the main reason for surgical resection in these patients. Current therapies can relieve inflammation in CD, but do not alter the natural history of the disease or its progression to intestinal fibrosis and obstruction. Taurine (2-aminoethanesulfonic acid) is a semi-essential amino acid that is not incorporated in proteins, plays an important role in several essential biological processes such as antioxidative properties, regulates intracellular Ca2+ concentration and membrane stabilization. Taurine has demonstrated antifibrotic effect in multiple organs including liver, kedney, pancreas, lung, etc. Meanwhile, it is found that taurine could ameliorate TNBS induced colitis in rats. However, there is rare report concerning its role in intestinal fibrosis.Aim:To investigate the effect of taurine on colonic fibrosis in rats with colitis induced by TNBS and its mechanism.Methods:1. Thirty-two SD rats were randomly divided into normal control group, model group, and low-dose and high-dose taurine groups (400mg/kg and 800mg/kg taurine respectively). 2. Rats in normal group were administrated with 0.9% NaCl solution enema, and rat colitis model was induced by TNBS enema in the latter three groups (administration of taurine began before one week of TNBS enema, and stopped as colitis model established).3. Morphology and disease activity index (DAI) were evaluated, colitis scores of macroscopic and histologic were performed, and colon length and weight were also measured. Levels of hydroxyproline, collagen typeⅠ, transforming growth factor-beta1(TGF-β1), and Smad3 protein and mRNA in colon tissues were examined.Results:1. Compared with control group, colon length of model group decreased and colon weight increased obviously(P<0.01); DAI, marcoscopic score and histologic score raised significantly(P<0.01); Markedly high levels of hydroxyproline, collagen typeⅠ, TGF-β1 and Smad3 were discovered(P<0.01).2. Intervention with taurine ameliorated the above indexes remarkably, especially with high-dose taurine. In this group, colon length increased and colon weight decreased (P<0.01); DAI, marcoscopic and histologic scores reduced(P<0.05, P<0.01, P<0.01 respectively); a low level of hydroxyproline contents was observed(P<0.05) in colon tissues, with an evident decrease in expression of collagen typeⅠ, TGF-β1 and Smad3(P<0.05).Conclusions:1. Taurine is effective in prevention of intestinal fibrosis induced by TNBS in rats.2. Antifibrotic mechanism of taurine seems to be mediated by the down regulation of TGF-β1 and the inhibition of TGF-β/ Smad3 pathway.