摘要目的 在雌性或雄性BALB/c小鼠制备Graves病动物模型,观察其促甲状腺素受体抗体(TRAb)滴度,TT4水平以及甲状腺组织的增生情况,探讨性别差异对成模的影响.方法 用表达TSH受体A亚单位的重组腺病毒免疫雌性或雄性BALB/c小鼠诱导Graves病,每3周免疫1次,共3次,末次免疫后4周取血,检测TRAb、TT4,剥离甲状腺行组织学检查.结果 雌性和雄性实验组小鼠TRAb阳性率均达到100%,两组之间抗体滴度无显著性差异.雌性及雄性实验组分别有75.0%,41.7%的小鼠发生甲亢,雌性实验组TT4水平明显高于雄性实验组并有统计学差异(P＜0.01),各组甲亢小鼠甲状腺组织出现明显增生.结论 利用表达TSH受体A亚单位的重组腺病毒免疫雌性、雄性BALB/c小鼠诱导Graves病动物模型,尽管两性TRAb抗体水平相似,但其甲亢发生率及程度存在一定的性别偏倚,提示雌性小鼠更易于模型的诱导.

abstractsObjective To investigate the effect of mice gender on the TSH receptor antibody(TRAb)titers, the levels of TT4,and the degree of thyroid hyperplasia by establishing an animal model of Graves′ disease in male and female BALB/c mice. Methods Male and female BALB/c mice were immunized with recombinant adenovirus expressing TSHRA subunit(Ad-TSHR289)to induce Graves′ disease. Animals were injected 3 times at intervals of 3 weeks. All mice were sacrificed 4 weeks after the last injection to obtain blood for measurement of TSHR antibody titers and TT4evels, and thyroid glands for histological examination. Results TRAb positive rates were 100% both in female or male mice. No significant difference was observed in titers of TRAb between them. The incidence of hyperthyroidism in female mice was higher than that in male mice, being 75.0% and 41.7% respectively. There was statistical difference in levels of TT4between females and males(P＜0.01). Mice with high TT4exihibited marked thyroid hyperplasia. Conclusion Despite TSHR antibodies were similar between female and male mice, the incidence and degree of hyperthyroidism showed sex bias in Graves′s animal model. The results indicated that it was easier to induce model in females than in males by immunizing BALB/c mice with Ad-TSHR289.