The Experimental Study Of The Effect And Mechnism Of NOD2 In The Intestinal Barrier In Ileal Pouchitis

Objective: Observe the intestinal barrier function in ulceritive colitis(UC)patients with pouchitis after ileal-pouch anal anastomosis(IPAA),and explore the effect and mechnism of NOD2 in the intestinal barrier.Methods: The colonoscopy and pathologic information of the pouch were collected in patients with ulcerative colitis(UC)who were present in Tianjin Medical University Genneral Hospital from January 2011 to December 2016.The patients who met the standards were paid a return visit.According to pouchitis disease activity index,the patients were divided into pouchitis group and non-pouchitis group.The UC patients who got non-operated treatment as well as normal terminal ileal mucosal were treated as control group.The intestinal barrier of pouchitis and non-pouchitis patients was observed by transmission electron microscope.The expressions of NOD2,Occludin and ?-defensin were detected by immunohistochemistry,and the correlational analysis was conducted.Results: Under electron microscope,in non-pouchitis patients,tight junctions and microvilli of cavity surface among epithelial cells are in arrangement rules,and there is no obvious exfoliate phenomenon of microvilli.While in pouchitis patients,the tight junctions are short and widen with disordered arranged microvilli;microvilli of cavity surface are in disordered arrangement with local exfoliation.And with the exacerbation of inflammation of the pouch,tight junctions and microvilli are destroyed more,normal tight junction are even invisible.Immunohistochemical analysis shows the expressions of NOD2 protein among UC patients without surgery treatment,population with normal pouch and pouchitis patients have obvious difference(M±SD(100%)is 0.720±0.007,0.607±0.005,0.461±0.016 respectively,P<0.01).The expression level is reduced significantly in pouchitis group and there exist statistical differences among pouchitis group and the other two groups(P<0.05,P<0.05).the expressions of Occludin among UC patients without surgery treatment,population with normal pouch and pouchitis patients have obvious difference(M±SD(100%)is 0.840±0.003,0.779±0.005,0.193±0.004 respectively,P<0.01).The expression level is reduced significantly in pouchitis group and there exist statistical differences among pouchitis group and the other two groups(P<0.05,P<0.05).the secretion of ?-defensin among UC patients without surgery treatment,population with normal pouch and pouchitis patients have obvious difference(M±SD(100%)is 0.850±0.001,0.773±0.004,0.600±0.013 respectively,P<0.01).The secretion decreases significantly in pouchits patients and there exist statistical differences among pouchitis group and the other two groups(P<0.05,P<0.05).Correlation analysis shows that in pouchitis group the expression of NOD2 is related with Occludin and ?-defensin respectively(r=0.671,P<0.01;r=0.628,P<0.01).Conclusion: The intestinal barrier function of ileal pouchitis is abnormal.The expression level of NOD2 is correlated with the inflammation level and the intestinal barrier function of pouch.And the mechanisms are discussed.The intestinal barrier disruption which is associated with NOD2 expression may locate in the important status of pouchitis pathogenesis.