Protective Effect Of Curcumin On Intestinal Mucosal Barrier In A Mouse Model Of Ulcerative Colitis

Background:Ulcerative colitis is a non-specific inflammatory bowel disease which mainly occured in colorectum,and diarrhea,abdominal pain,bloody diarrhea accompanied by tenesmus are the main clinical symptoms.As a persistent healing disease,the pathological lesion mainly involved in colorectal mucosa and sub-mucosa.UC was more common in the Western developed countries,however,the diagnosis of this disease out rate has increased and become more common in China.There is no complete description of the specific pathogenesis of UC,but a large number of clinical data and animal experiments have found that the disease is accompanied by obvious intestinal immune imbalance.In order to better study the disease and simulation the similar clinical pathological change,TNBS and DSS used to inducing colitis model were most common,moreover the DSS had a more simple operation and was closer to the clinical and pathological manifestations of,therefore it become nearly 20 years the most common enteritis model inducer.Curcumin was a kind of chemical component extracted from the roots of Zingiberaceae,Araceae plants,which containing turmeric about 3% ~ 6%,plant community in few second ketone pigment containing ketone compounds.An increasing number of experimental studies have suggested that curcumin had a significant control effect on UC.Intestinal epithelial lymphocytes constituted the immune barrier of the intestinal tract,which played a crucial role in contributing to mucosal homeostasis of intestine.It could promote the regeneration and repair of enterocytes through the production of KGF,TGF-? and IL-10,and protected the intestinal tract from the invading pathogens by secreting antimicrobial peptides.Other studies have reported that the subsets of IEL changed in intestinal specimens of UC patients.So We hypothesis that curcumin could protect the intestinal mucosa from inflammatory damages through modulating the subsets of IEL in a mouse model of ulcerative colitis,which provides the basis for the wide application of curcumin in the treatment of inflammatory bowel disease.Methods:1.Establishing the model of ulcerative colitis induced by DSS in mice,by DAI score,RT-PCR,HE staining,Ussing Chambers technology,to observe the inflammatory damage of colonic mucosa.2.According to the Control model,flow cytometry was used to detecting the changes of IEL subsets,on the other hand,the corresponding secretion of cytokines was observed with RT-PCR.3.DSS induced mice while giving curcumin treatment,the DAI score,RT-PCR,HE staining and Ussing chambers technology were used to detected the inflammatory responses changes in the intestinal mucosa,and using flow cytometry to observe the changes of colonic IEL subsets Results:1.Compared with the Control group,colonic mucosa in the DSS treatment group obviously fractured,loss,separated and increased permeability while DAI score increased significantly.Compared with the DSS group,DSS+Curcumin treatment group(80mg/ml curcumin)processing five days of colonic mucosal inflammation injury was to alleviate,colonic mucosa permeability and DAI score also decreased significantly.2.Compared with the Control group,the colonic mucosa in DSS group generated more inflammatory mediators and IEL secretion of protective cytokines significantly decreased.Compared with DSS group,DSS+Curcumin group,the intestinal mucosa destructive inflammatory mediators decreased obviously,however,IEL of protective cytokines expressed more.3.Compared with Control group,IEL subsets of CD8?? and ?? IEL in the DSS group decreased significantly while CD8?? and CD4+IEL increased.Compared with the DSS group,DSS+Curcumin group showed a higher of CD8?? and ?? IEL proportion and lower CD8??,CD4+IEL.Conclusion:1.Curcumin could attenuate the inflammatory damage of ulcerative colon model.2.Curcumin could decrease the level of inflammatory mediators in the intestinal tissue.3.Curcumin could regulate the intestinal IEL subsets,mainly for increased protective cell subsets of CD8??,?? IEL and decreased the aggressive cell subsets of CD8??,CD4+IEL.