基于网络毒理学,分子对接和分子动态模拟,探索可塑剂在肝损伤中的作用机制
Cheng Feng1, Luo Chun2, Shang KeLei1
1Fuyang Women and Children's Hospital, Fuyang, Anhui, China.
Scientific reports
|November 27, 2025
概括
像DMP,DEP和DOP这样的常见塑化剂可能会伤害肝脏. 这项研究使用了计算方法来识别关键的分子标,如FLT1和KIT,以及像PI3K-Akt这样的途径,涉及塑化剂诱导的肝损伤.
科学领域:
- 毒理学 毒理学 毒理学
- 计算生物学 计算生物学
- 分子生物学分子生物学
背景情况:
- 塑化剂 (DMP,DEP,DOP) 广泛使用,但与肝脏毒性有关.
- 了解塑化剂肝毒性的分子机制至关重要.
研究的目的:
- 为了研究塑化剂诱导的肝损伤的分子机制.
- 确定关键的分子标和参与肝毒性的途径.
主要方法:
- 使用了网络毒理学,分子对接和分子动力学模拟.
- 像ChEMBL,STITCH,GeneCards,OMIM和DisGeNET这样的数据库被用来识别目标.
- 进行了蛋白质-蛋白质相互作用网络和功能丰富分析.
主要成果:
- 在塑化剂和肝损伤之间确定了100个重叠的目标.
- 包括KRAS,KIT,LCK,NR3C1和FLT1在内的枢纽基因被优先考虑.
- 突出了PI3K-Akt,Ras信号传递和癌症中的蛋白质糖类等关键途径.
- 分子对接和MD模拟证实了塑化剂和FLT1和KIT等目标之间的稳定相互作用.
结论:
- 这项研究确定了关键的分子标 (FLT1,KIT) 和途径 (PI3K-Akt,Ras) 介导可塑剂肝毒性.
- 提供了关于可塑化剂诱导的肝损伤的新机制性见解.
- 强调了未来治疗干预的潜在目标.
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