综合网络毒理学和分子对接策略阐明铁亡机制,是乙二酸诱导心脏毒性的基础
Wan-Jing Zheng1, Run Zhang2, Gui-Dan Wang1
1Department of Anesthesiology, the Second Affiliated Hospital of Fujian Medical University, China.
Ecotoxicology and environmental safety
|February 5, 2026
概括
乙支柱酸盐 (ATBC) 暴露会通过触发细胞死亡途径铁亡,从而损害心脏细胞. 这项研究确定了与ATBC诱导心脏毒性相关的Caspase8,IDH2和MAPK14等关键标.
科学领域:
- 生物化学 生物化学
- 毒理学 毒理学 毒理学
- 心脏病学 心脏病学
背景情况:
- 像乙三酸 (ATBC) 这样的环境污染物对心脏健康构成风险.
- 铁亡,一种受调节的细胞死亡途径,在毒理学结果中越来越被认可.
- 了解ATBC的心脏毒性机制对于公共卫生至关重要.
研究的目的:
- 为了阐明ATBC的心脏毒性作用.
- 确定ATBC诱导的心脏损伤背后的分子机制,专注于铁亡.
- 确定涉及ATBC心脏毒性的关键分子标.
主要方法:
- 对数据库 (ChEMBL,STITCH,GeneCards,OMIM,FerrDb v2) 的生物信息分析,以识别ATBC和与铁死相关的基因.
- 使用STRING,cytoHubba和Cytoscape进行网络分析,以确定核心目标.
- 基因本体学和KEGG通路丰富分析.
- 分子对接模拟 (AutoDock) 来评估ATBC结合亲和力.
- 在体外实验中使用暴露于ATBC的心肌细胞进行实验.
主要成果:
- 确定了与ATBC相关的标和ferroptosis基因之间的25个共享基因.
- 确定了九个核心目标,精细化为三个关键目标:Caspase 8,IDH2和MAPK14.
- 通过分子对接,通过ATBC和核心目标之间确认了强大的结合亲和力.
- 证明ATBC会损害心肌细胞的活力,并在体外激活ferroptosis.
- 在ATBC暴露的心肌细胞中观察到卡斯帕酶8,IDH2和MAPK14的改变表达.
结论:
- 通过铁亡,ATBC在细胞水平上诱导心肌损伤.
- 卡斯帕酶8,IDH2和MAPK14是ATBC诱导心脏毒性的关键调解者.
- 为了解ATBC对心脏的影响和制定对策提供了一个框架.
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