【Animal Modeling】- Establish a humanized mouse model of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) gene, which provides an effective mouse model for the development and screening of tumor the

  Objective To establish an animal model suitable for evaluating the efficacy of traditional Chinese medicine compound and new drug development for ulcerative colitis with damp-heat syndrome, and to explore the difference and relationship between common ulcerative colitis and UC with damp-heat syndrome.

  Methods Twenty-four SD rats were randomly divided into blank control group, UC group, and UC+DH group, with 8 rats in each group. Except for the blank group, the UC group was induced by 5% DSS, while the UC+DH group was induced by "high-fat and high-sugar diet + alternating between hunger and satiety + drinking + high temperature and high humidity + 5% DSS" for 29 d. The general condition of the rats was observed daily, disease activity index (DAI) score and colon histopathological score (Geboes) were performed, and serum biochemical tests were performed to detect TG, CHOL, HDL_C, LDL_C, GLU, ALP, LDH, ALT, AST levels, DAO concentration in serum and MPO, MDA, GSH activity changes in colon, ELISA method to detect serum cortisol content and HSPs, IL-10, TNF-α, MIP- Expression of 1α and MIP-1β.

  Results Both models showed different degrees of intestinal inflammation, DAI score and Geboes index increased, and liver function was damaged to different degrees. Difference: compared with UC group, the above pathological changes were more serious in UC+DH group rats, in addition, TG, CHOL, LDL_C, ALP, ALT, AST, DAO in serum of UC+DH group rats were significantly higher than those in UC group. , Cortisol concentration increased significantly, serum HDL_C concentration decreased significantly (P < 0.05); the expression of HSPs, MPO, MDA, TNF-α, MIP-1α, MIP-1β in colon increased significantly, GSH in colon increased significantly and IL-10 levels were significantly decreased (P < 0.05).

  Conclusion Both UC models have intestinal mucosal injury and liver injury. The difference is that the damp-heat environment can aggravate DSS-induced intestinal mucosal damage in UC rats, and the mechanism may be related to pro-inflammatory, lipid peroxidation, and increased intestinal mucosal permeability.