中链化偏激素触发甲状腺激素合成,并干扰甲状腺中的线粒体功能
Lin Cheng1, Shuangshuang Chen1, Yun Luo2
1CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning 116023, China.
中链甲 (MCCP) 通过增加激素合成和损害线粒体活性来破坏甲状腺功能. 这项研究揭示了MCCP毒性机制,这对于风险评估至关重要.
科学领域:
- 环境毒理学环境毒理学
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 中链化 (MCCP) 是广泛存在的环境污染物.
- 对MCCP的毒性存在担忧,并建议将其列入斯德哥尔摩公约的清单.
- 对于MCCP的确切毒理机制,在很大程度上仍未被描述.
研究的目的:
- 为了研究MCCP对雌性Sprague-Dawley大鼠甲状腺的毒性影响.
- 使用转录组学和代谢组学阐明了MCCP诱导的甲状腺毒性背后的分子途径.
- 为基于机制的MCCP风险评估提供见解.
主要方法:
- 给大鼠使用MCCP (0.1-50 mg/kg体重/天).
- 甲状腺毛囊细胞的组织病理学检查.
- 测量血清甲状腺激素和相关调节因素.
- 转录和代谢分析以确定受影响的途径.
主要成果:
- 暴露于MCCP诱导了甲状腺毛囊细胞的基因病学变化,包括内分泌网膜和线粒体变化.
- 在较高剂量时观察到甲状腺激素释放激素,甲状腺刺激激素和甲状腺素的血清水平升高.
- 转录组分析揭示了参与甲状腺激素合成的基因的上调.
- 综合的奥米克数据表明,线粒体功能障碍是由脂肪酸氧化,克雷布斯循环和氧化酸化的变化引起的.
结论:
- 通过刺激甲状腺激素合成和破坏线粒体功能,MCCP对甲状腺表现出毒性.
- 观察到的代谢毒性可能与MCCP的含量有关.
- 这项研究为MCCP的行动模式和基于机制的风险评估提供了新的见解.
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