The Effect Of OSM In DSS-induced Experimental Colitis

BackgroundInflammatory bowel disease(IBD)is a chronic nonspecific inflammatory disease and the pathogenesis is unclear,including Crohn’s disease and ulcerative colitis.In recent years,the incidence of this disease in Asia is increasing.Many evidence suggests that intestinal barrier function plays an important role in IBD.OSM can increase cell proliferation and repair intestinal epithelium,and PGE2 can induce the production of OSM.However,the role of OSM in IBD and whether selective COX-2 inhibitors regulate the expression of OSM and affect the severity of colitis deserve further study.ObjectiveThe IBD animal model was established and the selective COX-2 Inhibitor-Celecoxib was used to intervene.The levels of serum TNF-α and IFN-γ were detected.The DAI and HI score were used to evaluate the degree of inflammation.The expression of OSM,COX-2,STAT3 and pSTAT3 in the colon tissue of mice were detected at the protein level.To investigate the effect of selective COX-2 inhibitors on the regulation of OSM and the role of OSM in colitis.MothodsSPF Male C57BL6 mice(6-8 week old,n=48)were randomly divided into 4 groups.(1)control group :given unrestricted diet.(2)DSS group :drinking 2.5% DSS solution for 8 days.(3)DSS + Celecoxib group: treated with Celecoxib(15mg/kg/d)on the basis of drinking DSS solution at the beginning of the third day.(4)Celecoxib(15mg/kg/d)group: treated with Celecoxib at the beginning of the third day.All the data was recorded by statistical software SPSS 22.0.All the measurement data were expressed in mean ± and standard deviation.Homogeneity of variance was used in the data of statistics analysis(Levene).The measurement data of multiple group were compared with single factor analysis of variance(ANOVA),and the comparison between two groups was performed with Bonferroni test.P<0.05 was considered statistically significant.ResultsDAI score of Mice Colitis in each group: Compared with Control group,DSS model group showed weight loss,diarrhea and bloody stool.The symptoms of DSS + Celecoxib group were severer than that of DSS group.DAI in DSS group was higher than that in Control group(P<0.05),DSS + Celecoxib group was higher than that in DSS group(P<0.05).There was no significant difference between Celecoxib group and Control group.HI score in each group: Compared with Control group,DSS group had congestion and edema of colon mucosa,epithelial cell injury,ulcer,different degrees of gland structure disappearance,crypt deformability,destruction and inflammatory cell infiltration.DSS + Celecoxib group was severer than that of DSS model group.HI in DSS + Celecoxib group was higher than that in Control group(P<0.05),DSS + Celecoxib group was higher than that in DSS group(P<0.05).There was no significant difference between Celecoxib group and Control group.The expression of TNF-α、IFN-γ in serum was detected by immunohistochemistry: DSS group was higher than Control group(P<0.05),DSS + Celecoxib group was higher than DSS group(P<0.05).There was no significant difference between Celecoxib group and Control group.The expression of OSM and COX-2 in intestinal tissue was detected by immunohistochemistry: DSS group was higher than Control group(P<0.05),DSS + Celecoxib group was lower than DSS group(P<0.05).There was no significant difference between Celecoxib group and Control group.The expression of OSM,Methods COX-2,STAT3,pSTAT3 in intestinal tissue was detected by Western Blot: DSS group was higher than Control group(P<0.05),DSS + Celecoxib group was lower than DSS group(P<0.05).There was no significant difference between Celecoxib group and Control group.Conclusions1.6-8 week old male C57BL/6 mice with 2.5%DSS solution given can induce colitis.2.Selective COX-2 Inhibitor Celecoxib can inhibit the expression of OSM in colon tissue,down-regulation of STAT3 and pSTAT3,and aggravate the DSS induced colitis.3.OSM is involved in the pathogenesis of DSS induced colitis in mice.