实验性猕猴Graves病模型的制备

A pilot study on inducing Graves＆#39; disease in rhesus monkeys

目的 用表达TSH受体A亚单位的重组腺病毒（A-sub-Ad）免疫雌性猕猴制备Graves病动物模型,观察其TT4、FT4、促甲状腺素受体抗体（TRAb）水平及甲状腺组织增生等情况.方法 将3岁雌性猕猴随机分为实验组和对照组,每组各6只.用A-sub-Ad及对照腺病毒（EGFP-Ad）于两侧股四头肌处肌肉注射免疫猕猴,每3周免疫1次,共5次.在造模期间动态取血,检测其TRAb、TT4、FT4水平.每周测定猕猴体重、心率并记录其变化.末次免疫4周后安乐死取甲状腺行组织学检查.结果 实验组中全部猕猴TRAb水平显著升高,50％猕猴血清TT4、FT4明显升高,甲状腺组织病理切片显示75％猕猴甲状腺显著增生,但无淋巴细胞浸润.与正常猕猴相比,甲状腺功能亢进猕猴体重明显下降,心率明显增快.结论 利用表达TSH受体A亚单位的重组腺病毒免疫与人类基因同源性很高的猕猴,成功制备Graves病动物模型,为人类Graves病进一步研究提供了良好的工具.

Objective To induce Graves＆#39; disease in rhesus monkeys,which would exhibit greater similarity to Graves＆#39; patients than previous rodent models.Methods Adult female rhesus macaques were injected intramuscularly with 6×1010 particles adenovirus expressing the A-subunit of TSHR （A-sub-Ad） or EGFP-Ad five times by three weeks intervals,and sera were prepared from blood samples collected at several time points during the immunization regimen.The animals were euthanized 4 weeks after the final injection to obtain blood,spleen cells,thyroid glands and other organs.Results After final immunization,the monkeys injected with A-sub-Ad showed characteristic of Graves＇disease.Compared to controls,all the test monkeys had significant higher TRAb levels,half of them had increased TT4 and FT4,and 75% developed goiter.Conclusion The non-human primate model of Graves＇disease was successfully established,which would provide an ideal tool for further understanding of the pathogenesis of Graves＆#39; disease in human.