甲状腺抗原诱导大鼠实验性自身免疫性甲状腺炎的研究

Induction of experimental autoimmune thyroiditis with xenogeneic autoantigens

目的观察人类甲状腺球蛋白（ｈＴＧ），人类甲状腺过氧化物酶（ｈＴＰＯ）以及豚鼠促甲状腺激素受体（ｇＴＳＨＲ）免疫诱导Ｗｉｓｔａｒ大鼠产生实验性自身免疫性甲状腺炎（ＥＡＴ）的过程。方法雄性Ｗｉｓｔａｒ大鼠共分四组，每组１０只，三组分别多次注射ｈＴＧ、ｈＴＰＯ、ｇＴＳＨＲ，第四组注射生理盐水作为对照。自０至１９１天，每次注射后，分别测定循环中ＴＴ３、ＴＴ４水平以及ＴＧＡｂ、ＴＰＯＡｂ、ＴＲＡｂ、ＴＳＡｂ和ＴＢＡｂ的活性；ＥＡＴ的严重程度采用甲状腺切片的显微镜观察进行评估。结果与正常组比较，实验组大鼠血清中存在高水平的ＴＧＡｂ、ＴＰＯＡｂ和ＴＳＡｂ；且甲状腺组织可见不同程度的淋巴细胞浸润，类似人类桥本氏甲状腺炎。此外，在ＴＳＨＲ组中不仅血清ＴＳＡｂ显著升高，而且甲状腺组织显示滤泡上皮增生、乳头状突起等Ｇｒａｖｅｓ’病（ＧＤ）的病理学特征。结论三种异源性抗原均能诱发正常Ｗｉｓｔａｒ大鼠产生ＥＡＴ，ＴＳＨＲ免疫的大鼠还显示了ＧＤ的倾向。

Objective The development of experimental autoimmune thyroiditis (EAT) was investigated by immunization of Wistar rats with human thyroglobulin (hTG) , human thyroid peroxidase (hTPO) and guinea pig thyroid stimulating hormone receptor (gTSHR). Methods Three groups of 10 male Wistar rats were injected repeatedly each with hTG, hTPO or gTSHR separately and a fourth group of 10 rats with saline as control. During day 0 to day 191, the serum levels of TT 3, TT 4 and activities of TGAb, TPOAb, TRAb, TSAb and TBAb were assayed after each immunization. The histological severity of EAT was assessed by microscopic evaluation of thyroid specimens. Results Compared with the control, high serum levels of TGAb, TPOAb and TSAb and thyroid lymphocytic infiltration, which was similar to human Hashimoto's disease (HT), were presented in the experimental groups. Interestingly, the rats immunized with TSHR displayed not only significantly raised serum TSAb but also some histological features of Graves' disease, including hyperplasia of follicular epithelium and papillary infoldings, etc. Conclusion All of the three antigens were able to elicit EAT in normal Wistar rats. The pathological status in rats immunized with TSHR was similar to human Graves' disease.