Establishment and analysis of NLRP3-/- mouse models of ulcerative colitis
10.3969/j.issn.1005-4847.2024.02.004
- VernacularTitle:NLRP3敲除小鼠溃疡性结肠炎模型的建立与分析
- Author:
Zhuhuan WANG
1
;
Erxin ZHANG
;
Qinwei ZHENG
;
Weiwei HAO
Author Information
1. 上海中医药大学附属曙光医院,上海 201203
- Keywords:
ulcerative colitis;
NLRP3-/- mice;
dextran sulfate sodium;
animal models;
modeling evaluation
- From:
Acta Laboratorium Animalis Scientia Sinica
2024;32(2):168-176
- CountryChina
- Language:Chinese
-
Abstract:
Objective To induce an NLRP3-/- mouse model of ulcerative colitis(UC)using different concentrations of dextran sulfate sodium(DSS)and different administration times,and to analyze and evaluate the advantages and disadvantages of the preparations to provide a more suitable animal model for the study of UC pathogenesis in humans and the development of therapeutic drugs.Methods Forty-eight male NLRP3-/- specific-pathogen-free mice were divided randomly into blank,2.5％7 d,3％7 d,and 3％5 d groups(n=12 mice per group).UC mouse models were induced using combinations of different concentrations and administration times of DSS.Body weight,DAI(disease activity index)score,hematoxylin and eosin(HE)staining,colon length,and related indicators(interleukin IL-6,tumor necrosis factor(TNF)-α,and tight junction protein(ZO-1))were observed and evaluated.Results(1)UC membrane type was induced in each group with different concentrations and administration times.(2)Mouse body weight decreased,the fecal occult blood became more positive,the DAI score increased,and more mice died with increasing DSS concentration and administration time.(3)Longer administration time and higher concentration of DSS were also associated with more severe damage to the intestinal mucosa,as shown by HE staining.(4)Immunohistochemistry showed that the inflammatory factors TNF-α and IL-6 were increased in the model group compared with the blank control group,while expression of ZO-1 was decreased compared with the blank group.Conclusions(1)Administration of 2.5％or 3％DSS for 7 days or 3％DSS for 5 days can induce UC in NLRP3-/- mice.(2)The combination of DAI score,HE staining,the detection of related indicators,and mouse survival rate indicated that NLRP3-/- mice treated with 3％DSS for 5 days produced the most suitable UC model to study the clinical manifestations and drug treatment of UC.
