6PPD和6PPD-的呼吸系统毒性机制:基于网络毒理学和分子对接的综合研究
Gang Li1, Dan Li2, Weibin Zhai1
1Department of Blood Transfusion, Naval Specialty Medical Center, Naval Medical University, Shanghai 200050, PR China.
Ecotoxicology and environmental safety
|June 12, 2025
概括
通过破坏线粒体和激活炎症通路,N-(1,3-二甲基) -N'--p-二胺 (6PPD) 和其衍生物6PPD- (6PPD-Q) 引起呼吸道毒性. 本研究确定了这些新兴环境污染物的关键分子标和机制.
科学领域:
- 环境毒理学环境毒理学
- 计算毒理学计算毒理学
- 分子生物学分子生物学
背景情况:
- 像6PPD和6PPD-Q这样的环境污染物对公众健康构成风险,特别是对呼吸系统.
- 6PPD/6PPD-Q呼吸道毒性背后的精确分子机制尚未完全理解.
研究的目的:
- 通过使用综合网络毒理学和分子对接,阐明6PPD和6PPD-Q诱导的呼吸道毒性的分子基础.
- 确定参与6PPD/6PPD-Q诱导的呼吸损伤的关键分子标和机制途径.
主要方法:
- 网络毒理方法包括ADMETlab 3.0,ProTox-II和多数据库挖掘 (BindingDB,ChEMBL,SwissTargetPrediction,TargetNet) 用于预测毒性和识别潜在目标.
- 进行交叉分析 (Venn图,STRING,Cytoscape) 和丰富分析 (DAVID),以确定化合物特定和共享的目标和相关途径.
- 采用分子对接和分子动力学模拟来确认目标结合亲和力和阐明相互作用模式,特别是与CYCS.
主要成果:
- EGFR和FYN分别被确定为6PPD和6PPD-Q的具体目标,NR3C1,MAPK14,RELA,CYCS和JAK2作为共同目标.
- 丰富分析揭示了与线粒体功能,氧化应激,亡以及神经活性联体受体相互作用的显著关联.
- 6PPD和6PPD-Q都表现出对关键毒性标的高亲和度结合,破坏线粒体电子运输链,诱导亡,并激活炎症NF-κB/JAK-STAT信号.
结论:
- 6PPD和6PPD-Q通过不同的但重叠的分子机制诱导呼吸道毒性,涉及线粒体功能障碍,亡和炎症.
- 这项研究为6PPD和6PPD-Q提供了一个比较的毒理学框架,确定了关键的分子标和途径.
- 计算毒理学策略对于评估新出现的污染物带来的环境健康风险是有价值的.
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