Thesis 2008: Mechanism of F- interference w thyroid hormones

Post Reply
admin
Site Admin
Posts: 3686
Joined: Tue Jan 18, 2005 10:25 pm

Thesis 2008: Mechanism of F- interference w thyroid hormones

Post by admin »

氟诱发甲状腺肿的分子病理学研究


张维东 , Masters  Advisor:张勇;刘国艳  

簡體中文

甲状腺肿大 ; 氟诱发 ; 分子病理学 ; 动物模型

氟(Fluoride)是一种全身性毒物,其对机体内分泌腺的影响已成为近年来的研究热点。有研究发现氟可导致动物甲状腺发生肿大,本试验选用SD大鼠80只,分为4组,通过在饮水中添加一定浓度梯度的氟化物,复制氟中毒致大鼠甲状腺肿模型。从氟影响甲状腺结构和功能的角度,初步阐述氟损伤大鼠甲状腺并致甲状腺肿大的分子机理。
本实验成功的复制出了不同程度氟致大鼠甲状腺肿模型。通过形态学、竞争放射免疫等方法测定反映甲状腺结构和激素分泌功能的一系列指标,结果发现氟引起甲状腺激素四碘甲腺原氨酸(3,5,3',5'-tetraiodothyronine,T4)、三碘甲腺原氨酸(3,5,3'-triiodothyronine,T3)合成和分泌障碍及甲状腺调节因子促甲状腺激素(Thyroid-stimulating hormone,TSH)等功能紊乱,直接影响整个机体的生长发育及新陈代谢过程。同时发现高氟导致大鼠甲状腺发生胶性或结节性肿大,破坏甲状腺的超微结构,尤其对细胞器的膜结构损伤最为严重。此结果是否定缺碘是引起地方性甲状腺肿的唯一因素理论的有力证明。实验进而系统阐述了氟损伤机体的分子机理。
运用RT-PCR、免疫荧光(imunofluorescence assay,IFA)等方法测定甲状腺相关酶类,以及部分相关蛋白和生长因子的表达与含量。结果发现甲状腺球蛋白(thyroglobulin,TG)、过氧化物酶(thyroidperoxidase,TPO)、钠碘转运体(sodiumiodide symporter,NIS)、促甲状腺激素受体(thyroid-stimulating hormone receptor,TSHR)、血管内皮生长因子(vascular endothelial growth factor,VEGF)等与甲状腺功能密切相关的指标均表现异常,氟引起自由基代谢紊乱,致NO生成的功能酶以及相关生长因子如一氧化氮合酶(inducible nitric oxide synthase,iNOS)和血管内皮生长因子(VEGF)表达受到影响发生显著变化,微血管增生,自由基和脂质过氧化物在甲状腺中蓄积,破坏了甲状腺滤泡上皮细胞结构和功能,干扰胶质的代谢,抑制甲状腺中碘的转运和有机化过程,干扰甲状腺功能酶系统如TPO和甲状腺Ⅰ型脱碘酶(type Ⅰ-deiodinase,Ⅰ-DI)的活性,破坏甲状腺激素合成和分泌的各个环节,引起甲状腺功能调节因子-TSH的代谢异常,最终导致甲状腺肿大。
结论:氟严重的破坏了甲状腺的结构和功能,最终在形态上,导致甲状腺胶性或结节性肿大。本论文在此基础上较为系统的阐述氟损伤大鼠甲状腺并致大鼠甲状腺肿大的分子机理。此项研究为全面阐明氟致大鼠甲状腺肿的分子机理提供了试验和理论基础,并为地方性甲状腺疾病的有效防治提供了新见解和新思路。

Fluoride is a systemic poison, and its influence on the secretory glands in the body has become a research hotspot in recent years. Some studies have found that fluorine can cause thyroid enlargement in animals. In this experiment, 80 SD rats were selected and divided into 4 groups. By adding a certain concentration gradient of fluoride in drinking water, the rat goiter model caused by fluorine poisoning was replicated. From the perspective of the influence of fluorine on the structure and function of thyroid, the molecular mechanism of thyroid injury and thyroid enlargement caused by fluorine in rats is preliminarily described.
    This experiment successfully reproduced different degrees of fluoride-induced goiter models in rats. A series of indicators reflecting thyroid structure and hormone secretion function were measured by methods such as morphology and competitive radioimmunity. The results showed that fluorine caused the thyroid hormone tetraiodothyronine (3, 5, 3 ', 5'-tetraiodothyronine, T4) , Triiodothyronine (3,5,3'-triiodothyronine, T3) synthesis and secretion disorders and thyroid regulatory factors Thyroid-stimulating hormone (TSH) and other dysfunction, directly affect the growth and development of the entire body And the metabolic process. At the same time, it was found that high fluoride causes the rat thyroid gland to develop colloid or nodular enlargement, destroying the ultrastructure of the thyroid gland, especially the most serious damage to the membrane structure of organelles. This result negates the theory that iodine deficiency is the only factor causing endemic goiter. The experiment then systematically elaborated the molecular mechanism of fluorine damage to the body.
    The expression and content of thyroid-related enzymes, as well as some related proteins and growth factors were determined by RT-PCR, immunofluorescence (IFA) and other methods. It was found that thyroglobulin (TG), peroxidase (thyroid peroxidase, TPO), sodium iodide symporter (NIS), thyroid-stimulating hormone receptor (TSHR), vascular endothelial growth Factors (vascular endothelial growth factor, VEGF) and other indicators closely related to thyroid function are abnormal. Fluoride causes disturbance of free radical metabolism, functional enzymes that cause NO production, and related growth factors such as nitric oxide synthase (iNOS) ) And the expression of vascular endothelial growth factor (VEGF) have been significantly affected, microvascular proliferation, free radicals and lipid peroxides accumulate in the thyroid, destroying the structure and function of thyroid follicular epithelial cells, interfering with the metabolism of glial, inhibiting The process of iodine transport and organicization in the thyroid gland interferes with the activity of thyroid functional enzyme systems such as TPO and thyroid type I deiodinase (type I-deiodinase, I-DI), destroys all links of thyroid hormone synthesis and secretion, and causes thyroid function The abnormal metabolism of regulatory factor-TSH eventually leads to goiter.
    Conclusion: Fluorine severely damages the structure and function of the thyroid gland, and eventually morphologically, causing thyroid glandular or nodular enlargement. In this paper, the molecular mechanism of thyroid injury and goiter caused by fluoride in rats is systematically described. This research provides an experimental and theoretical basis for fully elucidating the molecular mechanism of fluorine-induced goiter in rats, and provides new insights and new ideas for the effective prevention and treatment of endemic thyroid diseases.
Post Reply