动物造模,Graves病动物模型 z-bio 2022-11-02 310

　　Objective Based on the immune related mechanism of Graves disease, this study aims to explore the characteristics of different animal GD models by comparing the mouse and macaque GD animal models in our previous studies, and provide research tools for future immunotherapy based on the characteristics of different animal models.

　　Methods BALB/c mice were injected intramuscularly with recombinant adenovirus expressing thyrotropin receptor (TSHR) A subunit, once every three weeks, three times in total. The same recombinant adenovirus was injected into the muscle of rhesus monkey, and the virus dose of rhesus monkey was converted from the body weight and body surface area based on the mouse virus dose, once every three weeks, a total of five times. Four weeks after the last immunization, the mice and macaques were euthanized, and the peripheral blood, thyroid, spleen and other tissues were collected for determination of total thyroxine TT4, thyrotropin receptor antibody TRAb and immunological related indicators.

　　Results The TRAb level in the mouse model group (n=8) was significantly higher than that in the control group [(8.1 ± 0.6) IU/Ivs423.1 ± 61.4) IU/I], and the TT4 level in 6 mice was significantly higher than that in the control group [(57.1 ± 2.9) μ g/dL vs(96.7±13.8) μ G/dL, P<0.05], the incidence of GD hyperthyroidism was 75%. The levels of TT4 and FT4 in 3 rhesus monkeys in the rhesus monkey modeling group (n=6) were significantly increased, and the incidence of hyperthyroidism was 50%. In thyroid pathology, the follicular epithelium of mice (6/8) and rhesus monkeys (3/6) showed obvious hyperplasia, which was cubic or high columnar. Flow cytometry analysis showed that the proportion of Treg cells in the peripheral blood and spleen of the rhesus monkey model group was significantly lower than that of the control group (P<0.05), which was consistent with the result of the proportion of Treg cells in the spleen of the mouse model group (P<0.05). In addition, the weight of rhesus monkeys in the model group decreased (P<0.05) and the resting heart rate increased (P<0.05).

　　Conclusion Compared with the macaque GD model, the induction time of GD hyperthyroidism in the mouse model is shorter and the incidence rate is higher, but the GD macaque basic physiological and biochemical indicators and immune related indicators show more similar manifestations and mechanisms with human GD patients. In the future research to explore the pathogenesis of GD and evaluate new treatment schemes, we can choose more appropriate research tools according to the different characteristics of the two animal GD models.