Abstract:To induce NLRP3-/- mouse ulcerative colitis (UC) model using different concentrations of Dextran Sulfate Sodium (DSS) and administration time, and to analyze and evaluate the advantages and disadvantages of its preparation, in order to provide a more clinical animal model for the study of UC pathogenesis and the development of therapeutic drugs.Method: 48 NLRP3-/- mice of SPF level were randomly divided into groups and induced UC mouse models using a combination of different concentrations of DSS and administration time (blank group, 2.5% 7 days, 3% 7 days, and 3% 5 days). The physical weight, DAI score, HE staining, measurement of colon length and related indicator molecules (IL-6, TNF) of the mice were observed and evaluated- α Compare the effect of modeling with the expression level of tight junction protein.Result: 1. Each group was able to induce UC membrane type at different concentrations and administration times; 2. As the concentration gradient increases and the administration time prolongs, the physical weight of the mice decreases more significantly, the fecal occult blood is more positive, the DAI score is higher, and the mice die; 3. HE staining showed that the longer the time and the higher the concentration of DSS, the more severe the damage to the intestinal mucosal tissue in mice; 4. Using immunohistochemistry to detect inflammatory factors and tight junction proteins, compared to the blank group, the inflammatory factors (TNF-α) in the model group were detected,The expression levels of IL-6 and IL-6 increased, while the expression level of tight junction protein (ZO-1) decreased compared to the blank group.Conclusion: 1. NLRP3-/- mice can induce UC models under conditions of 2.5% 7 days, 3% 7 days, and 3% 5 days; 2. Combining DAI score, HE staining, and related indicators detection, as well as mouse survival rate, NLRP3-/- mice induced UC model under 3% DSS-5d conditions are more suitable for clinical manifestations of UC and more favorable for later drug intervention.