动物造模,Graves病动物模型 z-bio 2022-01-31 411

　　Purpose This study aims to start from the immune-related mechanisms of Graves disease, compare our previous studies of mouse and macaque GD animal models, and explore the differences in the characteristics of different animal GD models, and based on the characteristics of different animal models, provide research for new methods of immunotherapy in the future tool.

　　Methods BALB/c mice were injected intramuscularly with recombinant adenovirus expressing thyrotropin receptor (TSHR) A subunit, once every three weeks for a total of 3 times. The same recombinant adenovirus was used to intramuscularly inject rhesus monkeys. Based on the mouse virus dose, the virus dose of rhesus monkeys was converted by body weight and body surface area, once every three weeks, for a total of 5 times. Mice and macaques were euthanized four weeks after the last immunization, and peripheral blood, thyroid, spleen and other tissues were collected to determine total thyroxine TT4, thyroid-stimulating hormone receptor antibody TRAb and immunological related indicators.

　　Results The level of TRAb in the mouse model (n=8) was significantly higher than that of the control group [(8.1±0.6)IU/Ivs423.1±61.4)IU/I]. Among them, the TT4 level of 6 mice was significantly higher. The T4 level was significantly higher than that of the control group [(57.1±2.9)μg/dL vs (96.7±13.8)μg/dL, P<0.05], the incidence of GD hyperthyroidism was 75%. In the macaque model (n=6), the TT4 and FT4 levels of 3 macaques were significantly increased, and the incidence of hyperthyroidism was 50%. In thyroid pathology, both mice (6/8) and macaque (3/6) had obvious proliferation of follicular epithelium, which was cubic or tall columnar. Flow cytometry analysis showed that the proportion of Treg cells in the peripheral blood and spleen of the macaque model was significantly lower than that of the control group (P<0.05). This result is consistent with the result of the proportion of Treg cells in the spleen of the mouse model. (P<0.05). In addition, the modeled macaques also experienced a decrease in body weight (P<0.05) and an increase in resting heart rate (P<0.05).

　　Conclusion Compared with the rhesus monkey GD model, the mouse model of GD hyperthyroidism has a shorter induction time and a higher incidence, but the basic physiological and biochemical indicators and immune-related indicators of GD rhesus monkeys show more similar performance and mechanisms to human GD patients . In future studies to explore the pathogenesis of GD and evaluate new treatment options, we can choose more suitable research tools based on the different characteristics of the two animal GD models.