综合性网络毒理学,分子动力学和转录分析阐明了DEHP诱导的心血管功能障碍
Yi Guo1, Panpan Song1, Yanan Liu1
1College of Bioengineering and Biotechnology, Zhejiang University of Technology, 18th Chaowang Rd., Hangzhou 310014, China.
Toxicology research
|July 11, 2025
概括
甲基基甲酸盐 (DEHP) 暴露与心血管疾病 (CVD) 有关. 这项研究确定了关键的基因标,揭示了DEHP.
科学领域:
- 环境毒理学环境毒理学
- 心血管研究研究心血管研究
- 计算生物学 计算生物学
背景情况:
- 甲基基甲酸盐 (DEHP) 是一种广泛存在的环境污染物.
- 暴露于DEHP与心血管疾病 (CVD) 有关.
- 导致DEHP心脏毒性的分子机制尚不清楚.
研究的目的:
- 为了确定涉及DEHP诱导心血管病变的关键基因标.
- 阐明DEHP对心血管健康影响的分子机制.
- 探索减轻DEHP毒性的潜在治疗目标.
主要方法:
- 综合网络毒理学,分子对接和分子动力学模拟.
- 使用公共数据库 (STITCH,ChEMBL,GeneCards,OMIM) 对临床目标进行查.
- 对DEHP与已识别的基因标相互作用的分析和基因表达特征分析.
主要成果:
- 已经确定了十个核心基因候选者:BCL2,IL6,KRAS,TNF,MAPK1,MAPK3,CYP1A2,CYP2C9,CYP3A4,CYP3A5.3等.
- DEHP与KRAS,TNF,MAPK和CYP的相互作用是稳定的,这表明直接调节.
- 暴露于DEHP上调了BCL2和IL6,可能是间接通过与MAPK和TNF信号的途径交叉.
结论:
- KRAS,TNF,MAPK和CYP是DEHP与心血管功能障碍相关的直接分子标.
- 通过路径相互作用,BCL2和IL6通过路径相互作用间接参与DEHP心脏毒性.
- 这项研究提供了关于DEHP诱导的心血管损伤的见解,并确定了潜在的治疗点.
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