在斑马鱼中,HFPO-TA通过FABP3扰乱线粒体动力学来诱导心脏发育损伤
Xing Liu1, Mingzhu Xia1, Xinyi Wu1
1School of Public Health, Faculty of Medicine, Yangzhou University, Yangzhou 225009, China.
Environmental research
|February 13, 2026
概括
六烯酸氧化物三酸 (HFPO-TA) 通过破坏脂肪酸代谢和线粒体功能,导致斑马鱼的心脏缺陷. 向脂肪酸结合蛋白-3 (FABP3) 可能可以防止这些毒性影响.
科学领域:
- 环境毒理学环境毒理学
- 发展生物学 发展生物学
- 分子毒理学分子毒理学
背景情况:
- 六烯氧化物三酸 (HFPO-TA) 是一种可疑具有心脏毒性的PFOA替代品.
- 了解HFPO-TA对心脏发育的影响对于公共卫生至关重要.
研究的目的:
- 研究HFPO-TA诱导的心脏发育毒性的机制.
- 确定涉及HFPO-TA毒性的关键分子标和途径.
主要方法:
- 网络毒理学和分子对接以识别目标.
- 斑马鱼胚胎暴露模型来评估心脏毒性.
- 基因表达分析,线粒体动力学评估和亡试验.
- 基因淘汰研究中的CRISPR干扰 (CRISPRi).
主要成果:
- 在斑马鱼中,HFPO-TA暴露导致心周胀,心率增加和心脏基因表达改变.
- HFPO-TA上调了FABP3,抑制了PPARγ/PGC-1α,破坏了线粒体动力学,并诱导了亡.
- 抑制FABP3改善了HFPO-TA的毒性作用,恢复了正常的心脏发育和功能.
结论:
- HFPO-TA通过FABP3激活和PPARγ/PGC-1α抑制诱导心脏发育毒性.
- 线粒体功能障碍和亡是HFPO-TA心脏毒性的关键下游事件.
- FABP3是HFPO-TA心脏毒性的关键调解者,这表明它是潜在的治疗点.
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