Effects of NLRP3 gene knockout on mucosal barrier and inflammatory factors in mice with ulcerative colitis
10.3969/j.issn.1005-4847.2025.03.008
- VernacularTitle:敲除NLRP3基因对溃疡性结肠炎小鼠粘膜屏障及炎症因子的作用研究
- Author:
Yirong SHI
1
;
Erxin ZHANG
;
Xuantao QIAN
;
Weiwei HAO
Author Information
1. 上海中医药大学附属曙光医院,上海 201203;上海市中医药研究院脾胃病研究所,上海 200032
- Publication Type:Journal Article
- Keywords:
ulcerative colitis;
NLRP3 gene knockout;
mesalazine;
mucosal barrier;
inflammatory factor
- From:
Acta Laboratorium Animalis Scientia Sinica
2025;33(3):399-410
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism of NLRP3 gene knockout in relation to the abnormal mucosal barrier and inflammatory factors in ulcerative colitis(UC)mice.Methods Thirty-two NLRP3-knockout(NLRP3-/-)mice and 30 C57BL/6 wild-type(WT)mice were divided randomly into six groups:NLRP3-/-blank,NLRP3-/-model,NLRP3-/-mesalazine,WT blank,WT model,and WT mesalazine groups.Except for mice in the two blank groups,mice in the other groups were given 3％dextran sodium sulfate to drink freely for 5 days to establish an UC mouse model.After successful establishment of the model,mice in each group underwent intragastric administration of the respective solution for 7 consecutive days.The general condition,body weight,disease activity index(DAI)score,and colon length were observed and evaluated in each group.Histopathological changes in the colon were observed by hematoxylin and eosin staining.ZO-1,claudin-1,occludin,tumor necrosis factor(TNF)-αand interleukin(IL)-6 expression in colon tissue were detected by immunohistochemistry.Results(1)The DAI score was significantly higher in the NLRP3-/-model group compared with the WT model group on day 12,while colon length was significantly shorter and pathological injury of the intestinal mucosa was more serious.Expression levels of ZO-1,claudin-1,and occludin in colon tissue were lower whereas expression levels of TNF-α and IL-6 were significantly higher in the NLRP3-/-model group compared with the WT model group.(2)Regarding the two mesalazine groups,the DAI score was significantly higher and expression levels of ZO-1,claudin-1,and occludin in colon tissue were lower in the NLRP3-/-mesalazine compared with the WT mesalazine group on day 12.Conclusions Specific knockout of the NLRP3 gene makes mice more sensitive to UC.Compared with WT mice,NLRP3-/-UC mice have more severe mucosal barrier injury and release more inflammatory factors.Mesalazine could repair the mucosal barrier and reduce inflammation in NLRP3-/-and WT UC mice.Under the same experimental conditions,mesalazine repaired the mucosal barrier more effectively in WT compared with NLRP3-/-UC mice.
