The Effect Of Esomeprazole On Dextran Sulfate Sodium-induced Mouse Chronic Colitis

Objectives: To observe the effects of esomeprazole(ESO),one of proton pump inhibitors,on the mucosal inflammation in mice with chronic colitis induced by dextran sulfate(DSS),and to explore it’s possible mechanism.Methods: Fifty 8-week-old(19-21 g)C57BL/6 male mice were randomly divided into normal control group(group A/saline group)and intervention group(group B).The mice in group B were induced chronic colitis by DSS solution and then further subdivided into model group(group B1/ DSS+saline,salin ip),group B2(DSS+ESO 7d,ESO solution ip for 7 days),group B3(DSS+ESO 14 d,ESO solution ip for 14 days),group B4(DSS+ESO 21 d,ESO solution ip for 21 days).The general conditions(including the changes of diet,drinking water,stool and body weight)were recorded.At the deadline,the mice were anesthetized and sacrificed,and the colon length was generally scaled.The histopathological changes including epithelial dysplasia,abnormal crypt foci formation,and colonic inflammatory lesions in colonic mucosa were evaluated.The expression of nitric oxide synthase(iNOS,one of signale pathway-related moleculars)and TNF-α in colonic tissue were detected respectively by immunohistochemistry.The levels of inflammatory cytokines(including TNF-α,IL-1β,IL-4,IL-10 and IL-12)in colonic tissue were measured by ELISA.And Western Blot(WB)was used to detect the expression level of TLR4,MyD88,and NF-κB,in colonic mucosa,which involve in the TLR4-MyD88-NF-κB/iNOS signale pathway.Results:(1)ESO ip increased the disease activity index(DAI)and colonic inflammatory score,and shortened the colonic length in DSS-induced chronic colitic mice by a time-dependent way(p<0.05).(2)The colonic level of TNF-α,iNOS protein and pro-inflammatory cytokines(TNF-α,IL-1β,IL-12)increased significantly,with a decrease of IL-4 and IL-10 after ESO ip in DSS-colitic mice(p<0.05).(3)ESO ip upregulated significantly the expression of TLR4-MyD88-NF-κB/iNOS.Conclusion: Long-term ESO ip may lead to imbalance of pro-inflammatory cytokines and anti-inflammatory cytokines,and up-regulate the TLR4-MyD88-NF-κB/iNOS protiens,which may aggravate the colonic inflammation in DSS-induced colitic mice.