动物造模 z-bio 2022-08-23 364

　　Objective This study aims to start from the immune-related mechanism of Graves' disease, compare the mouse and macaque GD animal models in our previous studies, and explore the differences in the characteristics of different animal GD models, and based on the characteristics of different animal models, provide a new method for future immunotherapy. 

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

　　Results The level of TRAb 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 6 mice had significantly higher levels of TT4. The level of T4 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], and the incidence of GD hyperthyroidism was 75%. In the rhesus monkey model group (n=6), the levels of TT4 and FT4 were significantly increased in 3 rhesus monkeys, and the incidence of hyperthyroidism was 50%. In thyroid pathology, follicular epithelial hyperplasia was evident in both mice (6/8) and rhesus monkeys (3/6) model groups, which were cubic or tall columnar. Flow cytometry analysis showed that the proportion of Treg cells in the peripheral blood and spleen of the macaque model group was significantly lower than that of the control group (P<0.05), which was consistent with the proportion of Treg cells in the spleen of the mouse model group. (P<0.05). In addition, the rhesus monkeys in the modeling group also showed a decrease in body weight (P<0.05) and an increase in resting heart rate (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 basic physiological and biochemical indicators and immune-related indicators of the GD macaque show more similar manifestations and mechanisms to human GD patients. . In future studies to explore the pathogenesis of GD and evaluate new treatment options, we can choose more appropriate research tools according to the different characteristics of the two animal GD models.