从蛋白质和微生物组的角度来看,PCB中介毒性的性别依赖调制
Richa Singhal1,2, Zayna Qaissi3, Hao Zheng4
1Center for Cardiometabolic Science, University of Louisville, Louisville, KY, 40202, USA.
Scientific reports
|November 14, 2025
概括
多二 (PCB) 毒性的性别差异与明显的肝蛋白和肠道微生物组变化有关. 这项研究揭示了PCB如何对男性和女性产生不同的影响,突出了PCB毒性的肠肝相互作用.
科学领域:
- 环境毒理学环境毒理学
- 肝病学 肝病学是一种肝病学.
- 微生物组研究 微生物组研究
背景情况:
- 多双 (PCB) 是持久性有机污染物,已知有性依赖性肝毒性.
- 现有的机制无法充分解释这些性别差异,需要对肠肝轴参与的调查.
研究的目的:
- 为了研究PCB暴露引起的肝蛋白和肠道微生物组的性别特异性变化.
- 确定肠肝相互作用对性别特异性PCB毒性的贡献.
主要方法:
- 暴露于雄性和雌性C57BL/6J小鼠的Aroclor1260和PCB126.
- 使用LC/MS和肠道微生物组组成通过16S测序分析肝脏蛋白质组.
- 对酸受体 (AHR) 和肝X受体 (LXR) 激活的计算分析.
主要成果:
- 生物性别是肝脏蛋白质组差异和PCB肝脏反应的主要驱动因素.
- 暴露于PCB的女性显示肝脏AHR点增加 (例如CD36) 和增强的AHR/LXR激活.
- 暴露于PCB的男性表现出明显的肠道微生物群变化 (增加了Dehalobacterium) 和减少了肠道屏障基因表达.
结论:
- PCB 毒性表现出显著的性别特异性模式,涉及明显的肝脏和肠道微生物组变化.
- 雌性表现出与AHR和LXR通路相关的变化的蛋白质组概况.
- 男性表现出更明显的肠道微生物组变化和损害肠道屏障完整性,强调了肠肝相互作用在PCB毒性的作用.
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