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目的观察促甲状腺激素受体(TSHR)活性片段aa352-366的免疫调节作用,探讨TSHR分子结构与功能的关系。方法将血蓝蛋白(KLH)偶联的多肽KLH-TSHRaa352-366和多肽加受体的混合物KLH-TSHRaa352-366+gTSHR,间隔15d分两组分别注入BALB/c小鼠腹腔内,对照组注射生理盐水,测定各时相血清中总三碘甲状腺氨酸(TT3)、总甲状腺素(TT4)、促甲状腺激素受体抗体(TRAb)、促甲状腺激素受体刺激抗体(TSAb)、促甲状腺激素受体抑制抗体(TBAb)水平;第90天后处死动物,检测小鼠甲状腺组织TSHRmRNA水平及其病理变化。结果与各组自身0d的数据比较,多肽组小鼠血清TT3、TT4水平降低,TRAb升高;多肽加受体组TT3、TT4水平降低,TRAb和TBAb升高,而TSAb降低。此外,多肽加受体组甲状腺组织TSHRmRNA水平较正常组增高;多肽组小鼠甲状腺组织显示滤泡上皮细胞扁平、核缺失、皱缩及胶质浓缩等甲状腺功能减低的病理改变。结论hTSHRaa352-366刺激小鼠血清TRAb和TBAb的产生,阻断TSH与TSHR的结合,抑制三碘甲状腺氨酸(T3)、甲状腺素(T4)的分泌,引起甲状腺组织的病理改变,可能是TBAb在TSHR大分子上的抗原决定簇。
Objective To observe the immunomodulatory effect of aa352-366, an active component of thyrotropin receptor (TSHR), and to explore the relationship between the molecular structure and function of TSHR. Methods KLH-TSHRaa352-366, a mixture of KLH-conjugated peptide KLH-TSHRaa352-366 and KLH-TSHRaa352-366 + gTSHR, was injected into BALB / c mice intraperitoneally every 15 days. The control group was injected with The concentrations of total triiodothyronine (TT3), total thyroxine (TT4), thyrotropin receptor antibody (TRAb), thyrotropin receptor stimulating antibody (TSAb), thyrotropin (TBAb). Animals were sacrificed on the 90th day, and the TSHR mRNA level and pathological changes in the thyroid tissue were detected. Results Compared with the 0d data of each group, the levels of TT3 and TT4 in the serum of the mice in the polypeptide group decreased and the levels of TRAb increased. The levels of TT3 and TT4 in the peptide plus the receptor group were decreased, the levels of TRAb and TBAb were increased, and TSAb was decreased. In addition, TSHRmRNA level in thyroid tissue of the peptide plus recipient group was higher than that in the normal group. The thyroid tissue of the polypeptide group showed pathological changes of the hypothyroidism, such as flattened follicular epithelial cells, nuclear loss, shrinkage and glial condensation. Conclusion hTSHRaa352-366 stimulates the production of serum TRAb and TBAb in mice, blocks the binding of TSH to TSHR, inhibits the secretion of triiodothyronine (T3) and thyroxine (T4), and causes the pathological changes of thyroid tissue, which may be TBAb Epitopes on TSHR macromolecules.