肿瘤坏死因子α对Graves’病患者甲状腺细胞基因表达的影响  

Regulation of thyroglobulin and thyroid peroxidase gene transcription by TNFα in cultured thyrocytes from patients with Graves' disease

作　　者：蔡东升[1,2] 刘超[1,2] 覃又文[1,2] 刘翠萍 蒋须勤[1,2] 张忠邦 陈家伟 

机构地区：[1]南京医科大学第一附属医院 [2]上海第二医科大学附属瑞金医院

出　　处：《中华内分泌代谢杂志》1999年第1期31-34,共4页Chinese Journal of Endocrinology and Metabolism

摘　　要：目的研究肿瘤坏死因子α（ＴＮＦα）在有或无促甲状腺素（ＴＳＨ）存在时，对甲状腺培养细胞甲状腺球蛋白（ＴＧ）、甲状腺过氧化物酶（ＴＰＯ）基因转录的影响。方法运用细胞原代培养技术和ＮｏｒｔｈｅｒｎＢｌｏｔ分子杂交技术，观察不同剂量的ＴＮＦα对甲状腺细胞ＴＧ、ＴＰＯｍＲＮＡ表达的调节作用。结果（１）ＴＮＦα在０．０１Ｕ／ｍｌ时能够明显降低甲状腺细胞基础状况下ＴＧ、ＴＰＯｍＲＮＡ的水平，当ＴＮＦα处于１～１００Ｕ／ｍｌ时，ＴＧ、ＴＰＯｍＲＮＡ的水平几乎检测不出；（２）ＴＳＨ在１０ｍＵ／ｍｌ时显著提高甲状腺细胞表达ＴＧｍＲＮＡ，ＴＮＦα在０．０１～１Ｕ／ｍｌ剂量范围内对ＴＳＨ的该作用无明显影响，但当ＴＮＦα浓度在１００～１０００Ｕ／ｍｌ时，对ＴＳＨ的该作用表现为抑制效应。（３）ＴＳＨ在１０ｍＵ／ｍｌ时显著提高甲状腺细胞表达ＴＰＯｍＲＮＡ，ＴＮＦα在０．０１Ｕ／ｍｌ剂量范围内对ＴＳＨ的该作用无明显影响，但当ＴＮＦα浓度在１～１０００Ｕ／ｍｌ时，对ＴＳＨ的该作用表现为抑制效应。结论ＴＮＦα能够在基因转录水平上抑制甲状腺细胞基础合成ＴＧ、ＴＰＯｍＲＮＡ，并且ＴＮＦα在较高水平时能够拮抗ＴＳＨ促进ＴＧ、ＴＰＯｍＲＮＡ表达的作?Objective To study the effects of TNFα with or without TSH on the thyroglobulin (TG) and thyroid peroxidase (TPO) gene mRNA levels. Methods Thyrocytes were isolated from thyroid tissues of patients with Graves' disease and TNFα at different doses were added in the absence or presence of bovine TSH. Total RNA was extracted from thyrocytes using a single step method and it was electrophoresed and transferred to nylon filter. The filter was hybridized to TG, TPO and and GAPDH probes respectively and subjected to autoradiography. Results (1) Basal TG and TPO mRNA levels of thyrocytes were significantly decreased by TNFα of 0.01U/ml and were inhibited to undetectable level by TNFα of 1～100U/ml; (2) TNFα in the concertration of 0.01U/ml～1U/ml did not affect TSH induced TG mRNA levels while at the dose of 100～1000U/ml TNFα significantly inhibited TSH induced TG gene transcription; (3) TNFα in the concentration of0.01U/mldidnotaffectTSH induced TPO mRNA levels, but TNFα at 1～1000U/ml significantly decreased TSH induced TPO mRNA. Conclusion TNFα directly affects TG and TPO gene transcription in cultured human thyrocytes without TSH and TNFα does not affect TSH stimulated TG, TPO mRNA levels at lower doses while decreases these levels at higher doses.

关 键 词：肿瘤坏死因子Α GRAVES病 甲状腺细胞 MRNA 

分 类 号：R581.102[医药卫生—内分泌]