【摘要】 目的用表达TSH受体A亚单位(TSHR289)的重组腺病毒免疫近交系BALB／c雌性小鼠制备人类Graves病动物模型。方法AdMax法构建重组腺病毒(Ad-TSHR289)。将6-8周雌性BALB／c小鼠随机分为实验组和对照组。取已构建好的Ad-TSHR289、对照腺病毒(Ad-null)分别直接经胫前肌注射小鼠,每3周免疫1次,共3次,第3次免疫后8周采血,检测血清TSH受体抗体(TRAb)、TT4、TSH,剥离甲状腺,行石蜡包埋,切片,组织学检查。结果实验组中50％的小鼠TRAb水平显著升高,21．4％血清TT4水平明显升高,TT4升高的小鼠有不同程度的体重减轻,甲状腺组织病理切片显示:28．6％的小鼠甲状腺显著增生并有乳头状结构形成,但无淋巴细胞浸润。结论利用表达TSHR289的重组腺病毒免疫近交系BALB／c小鼠,成功地制备了Graves病动物模型,为Graves病的进一步研究提供了良好的工具。更多还原

【Abstract】 Objective To prepare an animal model of Craves’ disease by immunizing inbred BALB/c female mice with recombinant adenovirus (Ad-TSHR289) expressing the thyrotropin receptor (TSHR) A-subunit. Methods Ad-TSHR289 was constructed by the method of AdMax. Female BALB/c mice aged 6-8 weeks were divided randomly into experimental group and control group, and injected intramuscularly with Ad-TSHR289 and control adenovirus ( Ad-null) respectively three times at 3 week intervals. Blood samples were obtained 8 weeks after the third injection for TSHR antibody ( TRAb), TT4 and TSH assays. Their thyroids were removed for histological examination. Results 50% of immunized mice developed markedly high level of TRAb, and 21.4% had elevated T4 level. Those mice with raised TT4 showed weight loss to various extent. Histological examination of the thyroid revealed that 28.6% of immunized mice displayed follicular hyperactivity with hyperplasia and papillary poles protruding into the follicular lumen; and no lymphocytic infiltration was observed. Conclusion An animal model with some characteristics of human Craves’ disease is successfully prepared by immunization with recombinant adenovirus expressing TSHR A-subunit. It will provide a valuable tool for further study on the pathogenesis of Graves’ disease.更多还原