促甲状腺激素受体多肽片段aa352-366的特性  

Characterization of polypeptide fragment of thyroid stimulating hormone receptor aa352-366

作　　者：陈宁[1] 朱云娟[1] 黄丽娟[1] 叶静[1] 姚小梅[1] 沈炳玲[1] 戴玉杰[1] 刘欣[1] 陆凤先[1] 

机构地区：[1]天津医科大学病理生理教研室,300070

出　　处：《中国药物与临床》2005年第5期332-335,F003,共5页Chinese Remedies & Clinics

基　　金：国家自然科学基金资助项目(30370682)

摘　　要：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 The immunological effect of polypeptide fragment of thyroid stimulating hormone receptor(TSHR) aa352-366 was observed and the structure-activity relationship of TSHR molecule was studied. Methods The conjugate of TSHRaa352-366 with KLH( hemocyanin from keyhole limpets) and the mixture of TSHRaa352-366 and guinea pig TSHR (called gTSHR) were injected into abdomen of mice in above different groups each 15 days and the mice were given saline injection as control. The levels of total T3 (TT3), total T4 (TT4), thyroid stimulating hormone receptor antibody (TRAb), thyrotropin receptor stimulating antibody (TSAb) and thyrotropin receptor blocking antibody (TBAb) in serum of mice were measured. The animals were killed on the day 90, and two sides of thyroid were taken and the level of TSHR mRNA in thyroid tissue and the pathological changes in mice thyroid were detected. Results Comparing with the data in same group on day 0, the levels of both TT3 and TT4 were decreased, TRAb and TBAb increased, but TSAb decreased too in TSHRaa352-366 group. Otherwise, the level of TSHRmRNA went up in mixture group, and the thyroid follicle showed some pathological changes such as flatted epithelia, shrinkage or bacilliform karyon in some epithelia and condensed colloid material et al like hypothyroidism in TSHRaa352-366 group. Conclusion hTSHRaa352-366 may induce TRAb and TBAb in mice serum, and those antibodies will block TSH binding to TSHR, and inhibit the secretion of TT3 and TT4, also induce the pathological changes in thyroid tissue. So the conclusion is TSHRaa352-366 as an activated antigen may induce TRAb and TBAb, block the binding of TSH to TSHR, and then inhibit the secretion of both of TT3 and TT4. So TSHRaa352-366 may be an antigen determinant of TBAb on TSHR molecule.

关 键 词：促甲状腺激素受体 多肽片段 aa352-366 TSHR 血蓝蛋白 KLH 

分 类 号：R392[医药卫生—免疫学]