环境雌激素多氯联苯（PCBs）影响甲状腺干细胞增殖与分化的研究

项目名称： 环境雌激素多氯联苯（PCBs）影响甲状腺干细胞增殖与分化的研究

项目编号： No.81200577

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 徐书杭

作者单位： 南京中医药大学

项目金额： 23万元

中文摘要： 本实验组在前期研究中发现，多氯联苯（PCBs）作为一类环境雌激素，能引起原代甲状腺细胞凋亡，和小鼠体内慢性甲状腺炎标志物过氧化物酶抗体（TPOAb）增高、甲状腺素水平下降。而流行病学研究却发现，PCBs污染人群甲状腺肿瘤患病率明显增高。目前，对此尚无合理解释，近年来倍受关注的甲状腺肿瘤干细胞学说为解释这一现象提供新的途径。我们的前期研究发现，甲状腺干细胞可在生长因子刺激和悬浮无血清培养下维持未分化状态，雌激素明显影响促进其增殖，并降低其分化。因此，申请人认为存在于污染环境且具有类雌激素作用的环境雌激素多氯联苯（PCBs）亦能影响甲状腺干细胞的增殖与分化，进而参与甲状腺肿瘤的形成。该研究应用细胞培养等基础研究方法，探讨PCBs是否参与影响甲状腺干细胞的增殖与分化，并观察ER受体及受体后机制在其中扮演的角色，最后在体内实验观察PCBs是否导致甲状腺干细胞异常分化和肿瘤形成。

中文关键词： 甲状腺；干细胞；多氯联苯；甲状腺肿瘤；环境雌激素

英文摘要： We have proved that polychlorinated biphenyls(PCBs) might interfere the thyroid function and thyroid homeostasis by inducing apotosis of primary thyrocytes. In vivo, PCBs affect thyroid function via the induction of autoimmunity. However, the incidence of thyroid tumor is increasing in the population exposing to PCBs. The mechanism has not been fully understood. Recent researches of thyroid stem cells have opened a new pathway for understanding the physiological mechanisms controlling basic biological processes as well as disease mechanisms. The multipotentiality and self-renewal ability of the stem cells are controlled by stem cell niche providing a microenvironment, composed of cellular structures or extracellular matrix in undifferentiated stem cells. Our previous work demonstrated that estrogen has the potential to stimulate the proliferation and inhibit the differentiation of thyroid stem cells.PCBs, refered to as environmental estrogens, has been demonstrated to mimic the estrogenic effect. In view of that, the question was addressed if PCBs alters the functions of adult thyroid stem/progenitor cells during the proliferation or differentiation process, and induces outgrowth of stem cells and aberrant differentiation to transform thyroid nodules. In the current study, we have investigated: 1) the potential

英文关键词： Thyroid；Stem cells；Polychlorinated biphenyls (PCBs)；Thyroid tumor；Enviromental estrogens