双甲通过MAPK介导的类固醇激素失调来破坏脏代谢,通过转录和代谢组分析确定了这种失调
Rui Gao1,2, Jiangsong Ma1, Xinru Chen1,3
1School of Forensic Medicine, Shanxi Medical University, Jinzhong, Shanxi, China.
Scientific reports
|October 17, 2025
概括
双甲 (BPA) 通过破坏类固醇激素通路而导致脏损伤. p38 MAPK通路调节11β-HSD2的表达,影响BPA诱导的毒性中的皮质醇和阿尔多素水平.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 双甲 (BPA) 暴露很普遍,在尿液中可检测到的水平.
- 新出现的证据将BPA与亚临床毒性和代谢问题联系起来.
- BPA诱导的损伤的基因调节机制尚未完全理解.
研究的目的:
- 为了研究BPA暴露导致的慢性损伤的转录调节.
- 阐明BPA诱导的毒性背后的分子机制.
主要方法:
- 转录调节的生物信息学分析.
- 在小鼠模型中进行正子发射断层扫描/计算机断层扫描 (PET/CT) 成像.
- 组织病理学检查脏组织.
- 多omics集成 (转录组-代谢组).
- 用MAPK抑制剂进行分子对接和细胞检测.
主要成果:
- 在小鼠中,BPA的使用诱导了脏炎症和组织损伤.
- 组织病理学显示,管状上皮细胞脱皮和矩阵沉积.
- BPA扰乱了皮质醇生物合成,阿尔多素调节和MAPK信号传递.
- p38 MAPK调节11β-基类固醇脱酶2型 (11β-HSD2) 表达的调节,影响类固醇激素的合成.
结论:
- 由BPA引起的损伤涉及p38 MAPK介导的11β-HSD2.2的调节.
- 这一途径影响皮质醇代谢和阿尔多素合成.
- 类固醇激素生物合成与BPA毒性中MAPK调节有关.
- 这些发现为了解BPA诱导的损伤和风险评估提供了基础.
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