甲状腺抗原诱导大鼠实验性自身免疫性甲状腺炎的研究

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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 To observe the immunogenicity of human thyroglobulin (hTG), human thyroid peroxidase (hTPO) and guinea pig thyroid stimulating hormone receptor (gTSHR) to induce experimental autoimmune thyroiditis (EAT) in Wistar rats. Methods Male Wistar rats were divided into four groups (n = 10 in each group). The three groups were injected with hTG, hTPO and gTSHR multiple times, and the fourth group with normal saline as control. From day 0 to day 191, the TT3 and TT4 levels and the activities of TGAb, TPOAb, TRAb, TSAb and TBAb in the circulation were determined after each injection; the severity of EAT was assessed by microscopic observation of thyroid sections. Results Compared with the normal group, there were high levels of TGAb, TPOAb and TSAb in the serum of the rats in the experimental group. Thyroid tissues showed different degree of lymphocyte infiltration, similar to that of human Hashimoto’s thyroiditis. In addition, not only the serum TSAb was significantly increased in the TSHR group, but also the histopathological features of Graves’ disease (GD) such as follicular epithelial hyperplasia and papillary processes in thyroid tissues. Conclusion All three heterologous antigens can induce normal Wistar rats to produce EAT. TSHR-immunized rats also showed the tendency of GD.
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