对可塑化剂二甲基甲酸的人类肝毒性和机制的全面分析
Liu Shi1, Xianlin Zheng2, Xiaojuan Wei3
1Department of Gastroenterology, Luxian People's Hospital, No. 628, Longnao Avenue, Luxian County, Luzhou City, 646000, China.
Naunyn-Schmiedeberg's archives of pharmacology
|January 19, 2026
概括
暴露于二甲基甲酸盐 (DMP) 可能会通过影响免疫反应和转录引起肝毒性. DMP与SIRT1和RELA结合,影响IL-17和HIF-1信号通路,揭示了肝毒性的关键机制.
科学领域:
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
- 环境健康 环境健康
背景情况:
- 甲基甲基甲酸 (DMP) 是一种塑化剂,降解速度缓慢,对人类健康有潜在的毒性.
- 肝脏对新陈代谢至关重要,特别容易受到像DMP这样的毒素的影响,导致肝毒性.
研究的目的:
- 为了确定DMP的潜在分子点.
- 阐明DMP诱导的肝损伤背后的分子机制.
- 调查DMP与已确定目标的结合性亲和力.
主要方法:
- 使用多个数据库 (CTD,SwissTargetPrediction,TargetNet,GeneCards) 系统地识别DMP和肝损伤目标.
- 构建一个目标交互网络并提取核心集群.
- 基因本体学 (GO) 和基因和基因组 (KEGG) 丰富分析的京都百科全书.
- 分子对接以评估DMP和核心目标之间的绑定亲和关系.
主要成果:
- 确定了167个潜在目标和37个核心目标.
- 对GO的分析显示,它参与了免疫反应调节和转录因子活性.
- 凯格分析强调了IL-17和HIF-1信号通路的丰富.
- 分子对接显示DMP与SIRT1和RELA (<-5kcal/mol) 有着强烈的结合.
结论:
- 通过IL-17和HIF-1信号通路,DMP可能会诱导肝毒性.
- 与SIRT1和RELA等核心目标的结合是DMP毒性的关键机制.
- 这项研究增强了对DMP诱导的分子水平肝损伤的理解.
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