双相似物通过破坏甲状腺激素合成途径来诱导甲状腺功能障碍
Chao Hu1, Yeqing Xu2, Mingmin Wang3
1School of Public Health, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; School of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China; School of Engineering, Hangzhou Normal University, Hangzhou 310018, China.
双相似物会破坏甲状腺激素 (TH) 的平衡和功能. 暴露于小鼠的甲状腺结构和功能受损,表明这些常见化学物质暴露对人类健康的潜在风险.
科学领域:
- 内分泌学 在内分泌学.
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
背景情况:
- 双类类似物在消费品中普遍存在,其结构与甲状腺激素 (TH) 有相似之处.
- 人类广泛接触双醇引起了人们对甲状腺相关健康结果潜在干扰的担忧.
- 通过各种双相似物干扰TH合成并导致甲状腺功能障碍的精确机制仍然不完全理解.
研究的目的:
- 在小鼠模型中研究双相似物对甲状腺内分泌干扰的影响.
- 评估不同双类相应物对TH合成,甲状腺结构和功能的影响.
- 阐明双醇诱导的甲状腺功能障碍背后的机制.
主要方法:
- 在C57BL/6小鼠的实验中,小鼠在5周内接受了不同剂量的双相似物 (0.00220 mg/kgBW/d) 接触.
- 分析了血清甲状腺激素 (TSH) 水平,甲状腺毛囊上皮的高度和关键甲状腺相关分子的蛋白质表达.
- 采用T-Screen测试来评估TH-依赖于细胞增殖和基因表达的影响.
主要成果:
- 服用特定双相似物 (BPS,TBBPS) 显著提高了血清TSH水平,表明甲状腺功能障碍.
- 暴露于20mg/kgBW/d的双醇显著增加了甲状腺毛囊上皮的高度,表明结构损伤,TBBPS显示出强烈的影响.
- 双相似物降低了参与TH合成和功能的关键蛋白质 (thyrotropin受体,/同载体,铁氧化酶) 的调节,并在TH依赖的细胞增殖中表现出对抗性活性.
结论:
- 双相似物通过干扰TH合成途径诱导明显的甲状腺功能障碍.
- 在甲状腺中观察到的结构和功能变化凸显了双相似物对TH平衡的不良影响.
- 这些发现强调了与双相似物暴露在由甲状腺激素调节的整体生理过程中相关的潜在风险.
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