Therapeutic Effect and Mechanism of Smecta Combined with Mesalazine on Ulcerative Colitis in Rats
|Keywords||Inflammatory bowel disease Ulcerative colitis Smecta mesalazine tight junction protein|
Inflammatory bowel disease (Inflammatory bowel disease, IBD) is a kind of chronic non-specific inflammatory bowel disease whose etiology is not very clear, including Ulcerative colitis (Ulcerative colitis, UC) and Crohn’s disease (Crohn’s disease, CD). This disease is common in western countries,but the prevalence of IBD in our country is on the rise in recent years, mainly UC increased. The common drugs used for inflammatory bowel disease (CD, UC) including salicylic acid, glucocorticoid and immunosuppressants, mesalazine (mesalazine, trade name Salford) is a new type of5aminosalicylic acid, is the effective treatment of ulcerative colitis (ulcerative colitis, UC), wide application in clinical currently. The three drugs have certain effect, but there are still a series of problems of curative effect is not ideal, long course of poor compliance, side effects etc.. The intestinal epithelial cell layer and cell conjunction constitute the first barrier against the external environment. Over the past decade, there has been increasing recognition of an association between the pathophysiology of inflammatory bowel disease (IBD) and intestinal barrier function. IBD patient’s intestinal barrier function compromised. Barrier dysfunction can predispose and contribute to the pathogenesis and progression of IBD, and increase the risk of IBD patients relapse. Thus, we hypothesize that to increase the intestinal barrier function benefit for maintaining the immune balance and stimulating the reparation of the mucosa. The mesalazine was mainly to reduce the intestinal mucosal barrier damage indirectly through inhibition of inflammation, rather than directly repair the injury of intestinal mucosal barrier. Studies have shown that, Smecta can effectively repair chronic intestinal mucosal injury in patients with diarrheaOur hypothesis:Smecta might consolidate the intestinal mucosal barrier function by effectively repairing intestinal mucosa of patients with IBD, promote inflammation remission. Smecta combined with mesalazine in patients can get better treatment effect.Objective:In this study, according to observating the effect of Smecta combined with mesalazine to the intestinal barrier function inUC model of rats to make sure the effect and mechanism of Smecta combined with mesalazine treating ulcerative colitis in rats, and provide basis for clinical treatment of ulcerative colitis.Methods80male SD rats of clean grade (170-190g), were randomly divided into two groups:70rats in model group and control group with10rats. The model group rats daily drink water with3%DSS for7consecutive days and then drink distilled water for7days, to build the model of ulcerative colitis. The control group were treated with distilled water. The model group were randomly divided into4groups, respectively perfused with smecta, mesalazine,i mesalazine combined with smecta, distilled water for14days, observing the general condition of the rats.14days later,8rats..randomly selected from each group were perfused with lactulose and mannitol, collecting urine and analysised by high performance liquid chromatography to detect the change of rats’ intestinal permeability, execute all remaining survival rats and colon specimens were collected. Evaluating colonic pathological changes of intestinal, Occludin, respectively, Claudin3, ZO-1, Claudin2expression were determined by RT-PCR and Western Blot.Results.1The establishment of ulcerative colitis model:High performance liquid chromatography shows increased lactulose mannitol ratio, and increased rat intestinal permeability. Intestinal epithelial tight junction protein ZO-1, occludin, claudin3mRNA expression reduced, claudin2mRNA expression increased.2The groups given drugs treatment, the intestinal permeability measurement (L/M) results:control group<mesalazine combined with smecta group<mesalazine group<Smecta group<DSS group, Smecta ameliorate the intestinal permeability, mesalazine combined with smecta group is better than mesalazine combined with smecta group. DSS ulcerative colitis model perfused with mesalazine combined with smecta, mesalazine, Smecta after2weeks, SD rats intestinal epithelial tight junction protein composition changes,claudin2mRNA expression reduced compared with DSS group, the most obvious with Smecta group; claudin3mRNA expression upregulated than those in DSS group, especially mesalazine group; ZO-1, occludin mRNA expression increased than DSS group, especially mesalazine combined with smecta group. Claudin3, ZO-1Western blot is consistent with the results of RT-PCR..ConclusionNo matter symptom and clinical, DSS colitis in SD rats are highly reproducible and share most feature with human ulcerative colitis (UC). What’s more, DSS destructive SD rat’s intestinal barriers function and alter tight junction protein expression in rat intestine. DSS ulcerative colitis rats model perfused with mesalazine combined with smecta,mesalazine,smecta, epithelial tight junction protein expression changed with DSS group, thus affecting the intestinal mucosal permeability restoration ways of promoting the intestinal mucosa.