Background:Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease(IBD).Increasing evidences has proved that tight junction(TJ)ba...Background:Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease(IBD).Increasing evidences has proved that tight junction(TJ)barrier dysfunction is one of the pathological mechanisms of IBD.The aim of this study was to observe whether enhancement of TJ can decrease colitis recurrence.Methods:Eighty C57BL/6 mice were randomly divided into four groups including normal group,colitis group,sulfasalazine(SASP)treated group,and traditional Chinese drug salvianolic acid B(Sal B)treated group.Colitis was established in mice by free drinking water containing dextran sulfate sodium,after treatments by SASP and Sal B,recombinant human interleukin-1b(IL-1b)was injected intraperitoneally to induce colitis recurrence.Results:Compared with sham control,cell apoptosis in colitis group was increased from 100.85±3.46%to 162.89±11.45%(P=0.0038),and TJ dysfunction marker myosin light chain kinase(MLCK)was also significantly increased from 99.70±9.29%to 296.23±30.78%(P=0.0025).The increased cell apoptosis was reversed by both SASP(125.99±8.45%vs.162.89±11.45%,P=0.0059)and Sal B(104.27±6.09%vs.162.89±11.45%,P=0.0044).High MLCK expression in colitis group was reversed by Sal B(182.44±89.42%vs.296.23±30.78%,P=0.0028)but not influenced by SASP(285.23±41.04%vs.296.23±30.78%,P>0.05).The recurrence rate induced by recombinant human IL-1b in Sal B-treated group was significantly lower than that in SASP-treated group.Conclusions:These results suggested a link between intestinal mucosal barrier dysfunction,especially TJ barrier dysfunction,and colitis recurrence.The TJ barrier dysfunction in remission stage of colitis increased the colitis recurrence.This study might provide potential treatment strategies for IBD recurrence.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China(No.81600440)Dalian Support Program for High Level Talents(No.2017RQ017).
文摘Background:Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease(IBD).Increasing evidences has proved that tight junction(TJ)barrier dysfunction is one of the pathological mechanisms of IBD.The aim of this study was to observe whether enhancement of TJ can decrease colitis recurrence.Methods:Eighty C57BL/6 mice were randomly divided into four groups including normal group,colitis group,sulfasalazine(SASP)treated group,and traditional Chinese drug salvianolic acid B(Sal B)treated group.Colitis was established in mice by free drinking water containing dextran sulfate sodium,after treatments by SASP and Sal B,recombinant human interleukin-1b(IL-1b)was injected intraperitoneally to induce colitis recurrence.Results:Compared with sham control,cell apoptosis in colitis group was increased from 100.85±3.46%to 162.89±11.45%(P=0.0038),and TJ dysfunction marker myosin light chain kinase(MLCK)was also significantly increased from 99.70±9.29%to 296.23±30.78%(P=0.0025).The increased cell apoptosis was reversed by both SASP(125.99±8.45%vs.162.89±11.45%,P=0.0059)and Sal B(104.27±6.09%vs.162.89±11.45%,P=0.0044).High MLCK expression in colitis group was reversed by Sal B(182.44±89.42%vs.296.23±30.78%,P=0.0028)but not influenced by SASP(285.23±41.04%vs.296.23±30.78%,P>0.05).The recurrence rate induced by recombinant human IL-1b in Sal B-treated group was significantly lower than that in SASP-treated group.Conclusions:These results suggested a link between intestinal mucosal barrier dysfunction,especially TJ barrier dysfunction,and colitis recurrence.The TJ barrier dysfunction in remission stage of colitis increased the colitis recurrence.This study might provide potential treatment strategies for IBD recurrence.
