干扰素调节因子在自发免疫性甲状腺炎发病机制中的作用

The role of interferon regulatory factor in the etiology of autoimmune thyroiditis

目的 探讨干扰素调节因子 (IRF) 1在实验性自发免疫性甲状腺炎 (EAT)发病及进展过程中的作用。方法 对 6周龄NOD小鼠用佐剂混合的小鼠甲状腺球蛋白 (mTg)免疫 ,4周后用相同剂量mTg加强免疫。再过4周取甲状腺和血清样本。甲状腺组织做HE染色 ,分析EAT的发病率及重症度。应用酶免疫测定 (EIA)法测定血清T4 值 ,评估甲状腺功能。采用酶联免疫吸附测定 (ELISA)法测定血清抗小鼠甲状腺球蛋白抗体 (anti mT gAb)值 ,分析其结果 ,探讨与EAT重症度的关系。结果 Tg免疫组IRF 1+/ +,+/ - ,- / -小鼠均比对照组显示EAT的高发倾向。在EAT重症度上 ,Tg免疫组比对照组明显增加 ,差异有显著的统计学意义 ,但与IRF 1基因型无相关性。Tg免疫组anti mTgAb值比对照组上升 ,有统计学意义 ,但在IRF 1基因型之间未显示相关性。血清anti mTgAb值与EAT重症度之间显示正相关关系。Tg免疫组血清T4 值比对照组降低 ,有统计学意义 ,但在IRF 1基因型之间未显示相关性。结论 IRF 1- / -小鼠与IRF 1+/ +,+/ -小鼠均可诱发Tg免疫性EAT ,说明在Tg免疫性EAT的发病过程中IRF 1的作用不大 ,证明IRF 1缺陷NOD小鼠在桥本病模型的病态分析中非常有价值。

Objective To investigate the role of interferon regulatory factor(IRF)-1 in the development of experimental autoimmune thyroiditis(EAT). Methods Either thyroglobulin(Tg) or saline emulsified in an adjuvand was administered to mice at 6 and 10 weeks after birth. Thyroid tissue and sera were obtained from 14-week-old mice. HE staining has been emplyed to evaluate the incidence and severity of EAT.Serum anti-mouse thyroglobulin antibodies(anti-mTgAb) titers of mice was determined by ELISA and the relationship between EAT severity and anti-mTgAb titer was analyzed. The value of T4 in serum was determined by EIA for evaluation of the thyroid function.Results Tg-treated IRF-1+/+,+/-and-/-mice revealed higher incidence of the EAT than that of the control group.EAT severity of Tg-treated mice was significantly higher than that of the controlled, but was independent of the genotype of IRF-1. Anti-mTgAb titer of Tg-treated mice was significantly higher than that of the controlled, but was independent of the genotype of IRF-1. Serum anti-mTgAb titers was in proportion to the severity of the EAT. Serum T4 value of Tg-treated mice was significantly lower than that of the controlled,but was independent of the genotype of IRF-1.Conclusion Tg-immunised EAT could be induced in IRF-1-/-and+/+,+/-mice. These results suggest that IRF-1 plays a minor role in the pathogenesis of immunological EAT and IRF-1 lacking NOD mouse plays an important role in the analyses of the model of the Hashimoto's morbidity.