| OBJECTIVE:To investigate the effects of single Smecta or Mesalazine or both combination on intestinal epithelia tight junction in rats with ulcerative colitis between different time of treatment and the same time of different groups, and explore potential mechanisms of damages and recover in intestinal mucosa.METHODS:Eighty-two male SD rats were randomized into five groups:normal control group (n=10), model control group (n=18), smecta treatment group(n=18), mesalazine treatment group(n=18), smecta/mesalazine treatment group(n=18).After3days when rats were adaptation to feed, acute colitis was induced in rats using TNBS. Then the amount of drug to be administered in each respective treatment of rats is calculated according to human and rat body surface area conversion formula. The pathologic changes of colonic epithelium were observed by staining with HE and light microscope at5th day and12th day after intervention respectively. The expression of claudin2and occludin and zol proteins in intestinal mucosal epithelium in each group was detected by immunohistochemistry at5th day and12th day after intervention respectively. The expression of claudin2and occluding and zol of each group in intestinal mucosal epithelium in each group was detected at12th day after intervention by real-time PCR.RESULT:1.Make model sucessfully:The rats had diarrhea with bloody stools and weight loss about24hours after making model. Colon tissue stained with HE and by light microscope observation has mucosal ischemia and necrosis, big ulceration area and submucosal edema, accompanied by neutrophil infiltration, muscle also scattered neutrophil. At the same time, glands structural is damaged and goblet cells decreased.On five days treatment,2.ResuIst of immunohistochemistry at5th day after intervention:The expression of claudin2proteins in the intestinal epithelium is mesalazine/smecta group>model control group> mesalazine group>smecta group>normal control group. Compared with the model control group, the expression of claudin2in smecta group is in decrease (P<0.05), one in mesalazine/smecta group and mesalazien group is in increase (P>0.05). The expression of occludin proteins in the intestinal epithelium is normal control group> mesalazine/smecta group=model control group> mesalazine group> smecta group. Compared with the modelcontrol group, one in the other groups is in increase(P>0.05). The expression of zol proteins in the intestinal epithelium is normal control group> mesalazine/smecta group=model control group> mesalazine group> smecta group. Compared with the model control group, one in the other groups is in increase(P>0.05).3.Results of immunohistochemistry at12th day after intervention:The expression of claudin2proteins in the intestinal epithelium is model control group> mesalazine group> smecta group> mesalazine/smecta group> normal control group. Compared with the model control group, one in the other groups is in decrease(P<0.05).The expression of occludin proteins in the intestinal epithelium is mesalazine/smecta group> normal control group> smecta group> mesalazine group>model control group. Compared with the model control group,the expression of occludin proteins in the intestinal epithelium in mesalazine/smecta group and normal control group is in increase(P<0.05),one in smecta group and mesalazine group is not changes (P>0.05).The expression of the zol proteins in the intestinal epithelium is mesalazine/smecta group> normal control group> smecta group> mesalazine group>model group. Compared with the model control group, the expression of zol in mesalazine/smecta group and smecta group is in increase(P<0.05),one in mesalazine group is in increase(P>0.05).4.Results of RT-PCR at12th day after intervention:The expression of cludin2proteins in the intestinal epithelium is model control group> mesalazine group> smecta group> mesalazine/smecta group. Compared with model control group, the expression of cluadin2in other groups is in decrease(P<0.05). The expression of occludin proteins in the intestinal epithelium is mesalazine/smecta group> smecta group> mesalazine group>normal control group> model control group. Compared with the model control group, the expression of occludin in the other control groups is in increase(P>0.05).The expression of zol proteins in the intestinal epithelium is mesalazine/smecta group> smecta group> mesalazine group>normal control group> model control group. Compared with the model control group, the expression of occludin in the other control groups is in increase(P<0.05).CONCLUSION:1.Intestinal tight junction protein claudin2, occludin, zol are all involved in the pathogenesis of ulcerative colitis.2.The ulcerative colitis treated with Single mesalazine or smecta or both combination are all effective. The combination of mesalazine and smecta is the best.3. The anti-inflammation of mesalazine play a dominant role in early stage of ulcerative colitis, smecta can support mesalazine to make the expression of claudin2down-regulation, occludin and zol up-regulation. When mesalazine play a role in anti-inflammation, smecta as the intestinal mucosal protective agent can reduce the absorption of exogenous harmful substances which damage the intestinal barrier to cure the ulcerative colitis better. |
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