通过综合网络毒理学阐明PFAS暴露对糖尿病的影响
1Departments of Endocrinology, Chongqing General Hospital, Chongqing, China.
Toxicology mechanisms and methods
|August 14, 2025
概括
环保污染物中含有和多基物质 (PFAS) 的污染物会破坏与糖尿病相关的基因功能和通路. 这项研究揭示了PFAS暴露.
科学领域:
- 环境毒理学环境毒理学
- 分子生物学分子生物学
- 代谢性疾病研究研究.
背景情况:
- 和多醇基物质 (PFAS) 是广泛存在的环境污染物.
- 暴露于PFAS与各种健康问题有关,包括代谢障碍,如2型糖尿病 (T2DM).
- 导致PFAS引起的糖尿病的确切分子机制尚不清楚.
研究的目的:
- 调查PFAS暴露影响糖尿病的分子机制.
- 为了确定关键的基因和受PFAS暴露影响的途径,与糖尿病病理生理学相关.
- 探索在与PFAS相关的代谢中断中发现的基因的潜在诊断价值.
主要方法:
- 使用了网络毒理学和功能基因组学方法.
- 使用比较毒基因组学数据库 (CTD) 分析与糖尿病相关的基因表达数据集 (GSE25724).
- 不同基因表达分析,通路丰富,ssGSEA,PPI网络构建,免疫细胞透分析,分子对接和HepG2细胞验证.
主要成果:
- 确定了34个与糖尿病和PFAS暴露相关的差异表达基因 (DEGs).
- 受影响的关键途径包括脂肪基因信号传递,胰岛素分泌和葡萄糖平衡;炎症途径受到上调,而代谢途径受到下调.
- ATP2A2,INS和NFE2L2被确定为关键的枢纽基因,在HepG2细胞中因PFAS暴露而显著下调,具有强大的诊断潜力 (AUC>0.88).
结论:
- 暴露于PFAS显著破坏了关键的基因功能和涉及糖尿病的生物学途径.
- 该研究强调了PFAS等环境毒素对代谢健康的重大影响.
- 需要进一步的研究来阐明PFAS在糖尿病发病过程中的作用,并制定有针对性的干预措施.
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