中文摘要：

目的对比促甲状腺素受体（TSHR）质粒DNA（pcDNA3．1-TSHR）及TSHRA亚单位重组腺病毒（Ad—TSHR289）诱导Graves病动物模型的效率，研究造模持续时间对Ad—TSHR289诱导的Graves病甲状腺功能亢进（甲亢）及相关指标的影响。方法分别设质粒组和病毒组。质粒组：将21只雌性BALB／c小鼠随机分为造模组（12只）、对照组（9只），造模组给予皮内注射pcDNA3．1-TSHR50μg，每3周1次，共免疫3次，末次免疫后4周处死小鼠，取血测TSHR抗体（TRAb）、总T。，剥离甲状腺行组织学检查。对照组给予等剂量的pcDNA3．1注射。病毒组：将52只雌性BALB／e小鼠分为10周造模组（8只）、14周造模组（10只）、18周造模组（8只）并分别设对照组（依次为8只／组、10只／组、8只／组），造模组给予Ad．TSHR289肌肉注射，每3周1次，共3次，末次免疫后4周、8周、12周依次处死小鼠，测定血清TRAb、总T4水平并观察甲状腺组织病理变化。对照组给予等剂量的Ad．1aez以相同方式处理。另设8只小鼠分别于3次免疫前后检测TRAb动态变化。结果质粒造模组只有2只小鼠出现较弱的TSHR抗体反应，无总T。水平的升高及甲状腺组织增生性改变。病毒10周造模组所有小鼠均出现了高水平的TRAb[（807．65±136．33）U／L]、8只小鼠中有6只小鼠发生甲亢并伴有甲状腺组织增生性改变。14周造模组TRAb水平[（650．12±192．88）U／L]、甲亢发生率（3／10）低于10周造模组，甲状腺增生性改变程度有所减轻，但其阳性率无降低。18周造模组8只小鼠中只有2只TRAb滴度出现轻度的升高，没有小鼠总T4水平高于正常，2只小鼠甲状腺组织轻度增生。进行TRAb滴度动态观察的小鼠抗体水平和不同时间的造模组呈现相似趋势。结论Ad—TSHR289诱导的Graves病动物模型重复性好，甲亢发生率高，仍是目前较为理想的研究工具。该模型持续时?

英文摘要：

Objective To compare tile efficacy of Graves disease animal models induced by thyroid stimulating hormone receptor （TSHR） plasmid DNA （pcDNA3.1-TSHR） and by TSHR A subunit recombinant adenovirus（Ad-TSHR289） , and to investigate the influence of duration for preparing animal model induced by Ad-TSHR289 on Graves hyperthyroidism and its related indices. Methods The plasmid group and the adenovirus group were set up respectively. The plasmid group： 21 female BALB/c mice were randomly divided into model group （n = 12 ） and control group （n = 9 ）. The model group were injected intradermally with pcDNA3.1-TSHR 50 p~g, once every 3 weeks, totally 3 times. Then 4 weeks after the last immunization, the mice were euthanized to obtain blood for testing TSHR antibody （TRAb） , total T4, and thyroid tissue for histological examination. The controls were injected with the same dose of pcDNA3.1 in the same way. The adenovirus group： 52 female BALB/c mice were divided into 10-week model group （n = 8）, 14-week model group （ n = 10） and 18-week model group （ n = 8 ）, and the respective controls （ n = 8, n = 10, n = 8） were set up. All model groups were injected intramuscularly with Ad-TSHR289, three times at three weekly intervals. Then the mice were euthanized at 4, 8 and 12 weeks to test TRAb, total T4 level and to observe the change of thyroid histology. The controls were treated with the same dose of Ad-lacz in the same way. Another 8 mice were scheduled to test the dynamic variation of TRAb before and after the 3 times immunization. Results In the plasmid model group, only two of 12 mice developed weak antibody responses against TSHR, and no elevated total T4 level and no hyperplasia changes of thyroid were observed. In the 10-week model group, all mice had high level TRAb [ （807. 65 ± 136. 33 ）U/L] , Six-eighths mice had hyperthyroidism exhibited hyperplasia changes. In the lg-week model group, the TRAb level [ （650. 12 ±192. 88）U/LI and the incidence of hyperthyroidism ?