Mechanism of mesalazine ameliorating colonic barrier function in mice with ulcerative colitis through Wnt1 pathway
10.3969/j.issn.1000-484X.2024.12.007
- VernacularTitle:美沙拉嗪通过Wnt1通路改善溃疡性结肠炎小鼠结肠屏障功能的机制研究
- Author:
Xiaohong QIN
1
;
Mengyuan WANG
Author Information
1. 锦州医科大学研究生培养基地,锦州 121001
- Keywords:
Mesalazine;
Ulcerative colitis;
Colonic barrier;
Wingless-type mouse mammary tumor virus integration site 1 signaling pathway
- From:
Chinese Journal of Immunology
2024;40(12):2500-2505
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate effect of mesalazine(MSLZ)on improvement of colonic barrier in mice with ulcerative colitis(UC),and its regulatory mechanism on wingless-type mouse mammary tumor virus integration site1(Wnt1)signaling pathway.Methods:C57BL/6 mice were randomly divided into normal control group(Control),model group(UC),MSLZ group and MSLZ+sh-Wnt1 group.Except for Control group,other groups were treated with sodium dextran sulfate(DSS)to establish UC model.Mice in Control,UC and MSLZ groups were intraperitoneally injected 5×109 pfu/ml NC-shRNA.Mice in MSLZ+sh-Wnt1 group were intraperi-toneally injected 5×109 pfu/ml shRNA-Wnt1.Mice in MSLZ group and MSLZ+sh-Wnt1 group were gavaged with 400 mg/kg MSLZ every day,and mice in Control and UC groups were gavaged with sterile distilled water of same dose every day.Colon length of mice in each group was detected.Kit was used to detect contents of D-lactate(D-LA),lipopolysaccharide(LPS)and activity of diamine oxidase(DAO)in serum of mice in each group.TUNEL staining was used to detect apoptosis in colon tissue of mice in each group.Immunohistochemistry was used to detect expressions of mucin 2(MUC2)and Occludin in colon tissues.Western blot was used to detect expressions of Wnt1,β-catenin,B cell lymphoma-2(Bcl-2)and Bcl-2 associated X protein(Bax).Results:MSLZ could signi-ficantly increase length of colon,increase expressions of MUC2,Occludin,Wnt1,β-catenin and Bcl-2 in colon tissue,decrease levels of D-LA,LPS,DAO in serum,cell apoptosis rate and expression of Bax in colon tissue,while MSLZ+sh-Wnt1 could partially reverse protective effect of MSLZ on colon barrier function(all P<0.05).Conclusion:MSLZ can inhibit apoptosis of colon mucosa in UC mice,alleviate pathological damage of colon tissue,and ameliorate barrier function of colon mucosa,which may be related to activation of Wnt1 signaling pathway.