Gs蛋白α亚基与毒性多结节性甲状腺肿自主功能性的研究  

Relationship between Gene Mutation in Gsα and Autonomous Function of Toxic Multinodular Goiter

作　　者：魏云浩 王凤军[1] 刘连新[1] 姜洪池[1] 孙静[1] 

机构地区：[1]哈尔滨医科大学附属第一医院,黑龙江哈尔滨150040

出　　处：《现代生物医学进展》2016年第1期67-71,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(30571615)

摘　　要：目的:检测TMG(毒性多结节性甲状腺肿:Toxic Multinodular Goiter)患者甲状腺细胞中的Gsα基因突变情况,讨论其与TMG细胞自主功能性的关系。方法:将16例TMG患者手术切除标本中甲状腺结节组织及其作为对照组的结节周围正常的甲状腺组织,分别于光镜电镜下观察细胞行为,提取DNA,对目的基因片段进行扩增聚合酶链反应(PCR)反应及DNA测序分析。结果:于光镜及电镜下可观察到TMG细胞的滤泡大小不等,滤泡上皮呈高柱状,增生明显,粗面内质网高度扩张,高尔基体发达,核糖体丰富,呈高功能状态。16例TMG标本中,5例发现第10外显子点突变,其中:2例为第274位的赖氨酸密码子AAG的第一个碱基A的缺失,使对应赖氨酸表达异常,3例为第279位的天冬酰胺的密码子AAC的第一个碱基A的缺失,对应天冬氨酸表达异常。对照组未发现Gsα基因突变。结论:TMG患者Gsα基因突变可导致Gsα/TSHR/c AMP信号通路异常,使细胞产生自主高功能状态,是导致TMG自主功能性发生的重要因素。Objective： To detect the gene mutation in Gsα and the relationship with autonomous function of TMG（toxic multinodular goiter）. Methods： Nodular specimens were obtained from 16 cases diagnosed as TMG（toxic multinodular goiter）, with normal thyroid specimens adjacent to the nodules as control. Cell behaviors were observed by using both optical microscope and electron microscope.Genomic DNAs were isolated from thyroid nodules and normul tissues of 16 TMGs. After amplifying the related regions, the precise localization of the mutations was identified by automatic DNA sequence analysis. Results： Thyroid follicular cell were observed with various size, hyperplasia of columnar follicle epithelial cell, expansion of rough endoplasmic reticulum, developed Golgi apparatus and abundance of ribosome. Exon 10 mutations of Gsα were identified in 5 of 16 TMGs. Two samples had deletion mutation in the first basic group of lysine codon（AAG）which expressed abnormally. Three samples had deletion mutation in the first basic group of aspartic acid codon（AAC）which expressed abnormally. Conclusion： The Gsα mutations play a certain role in abnormal expression of Gsα/TSHR/c AMP signal path which result in autonomous function of TMG cells.

关 键 词：基因突变 自主功能性 G蛋白 

分 类 号：R581[医药卫生—内分泌] R34[医药卫生—内科学]