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斑马鱼幼体可作为筛选干扰哺乳动物甲状腺形态发生和功能的化学物质的替代系统。

Zebrafish eleutheroembryos as an alternative system for screening chemicals disrupting the mammalian thyroid gland morphogenesis and function.

机构信息

Institute of Environmental Assessment and Water Research (IDÆA-CSIC), Jordi Girona 18, 08034 Barcelona, Spain.

出版信息

Reprod Toxicol. 2012 Apr;33(2):188-97. doi: 10.1016/j.reprotox.2011.09.001. Epub 2011 Sep 24.

DOI:10.1016/j.reprotox.2011.09.001
PMID:21978863
Abstract

The importance and irreversibility of the effects of thyroid hormone deficiency on human brain development highlight the importance of identifying environmental agents that interfere with thyroid gland morphogenesis and function. Zebrafish eleutheroembryos are currently used by many pharmaceutical companies in drug discovery as a vertebrate model, not subjected to regulations for animal experiments, that provides an intermediate step between in vitro and rodent assay. The mechanisms of zebrafish thyroid development are generally comparable to those in humans, and moreover, molecular and functional studies of zebrafish thyroid follicles have demonstrated a high degree of conservation with upper vertebrates, opening up the possibility of designing alternative methods for screening individual chemicals and mixtures that impairing thyroid gland morphogenesis and/or function. Analysis of the intrafollicular thyroxine-content of zebrafish larvae exposed to potential disruptors has proved to be a reliable, physiologically relevant endpoint to estimate effects of chemicals on the mammalian thyroid gland.

摘要

甲状腺激素缺乏对人类大脑发育的重要性和不可逆转性突出表明,有必要确定干扰甲状腺形态发生和功能的环境因素。斑马鱼幼鱼目前被许多制药公司在药物发现中用作脊椎动物模型,不受动物实验法规的限制,为体外和啮齿动物检测之间提供了一个中间步骤。斑马鱼甲状腺发育的机制通常与人类相似,此外,斑马鱼甲状腺滤泡的分子和功能研究表明与高等脊椎动物具有高度的保守性,为筛选可能破坏甲状腺形态发生和/或功能的个体化学物质和混合物的替代方法开辟了可能性。分析暴露于潜在干扰物的斑马鱼幼虫的滤泡内甲状腺素含量已被证明是一种可靠的、具有生理相关性的终点,可用于估计化学物质对哺乳动物甲状腺的影响。

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