网络毒理学与分子对接技术相结合,探索导致肝损伤的阿马托克辛的分子机制
Chenglin Wang1, Xin Wang2, Yaxing Deng1
1Department of Emergency Medicine, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District, Luzhou, Sichuan, China.
Scientific reports
|July 18, 2025
概括
毒素通过与SP1和CNR1结合而导致肝损伤,破坏细胞过程并导致亡. 早期诊断和治疗对于生存至关重要.
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:
- 氨毒素是高度有毒的真菌化合物,以其稳定性和耐药性而闻名.
- 它们通过抑制核酸和蛋白质合成,导致严重的肝脏和丧症.
- 及时诊断和干预对于预防多器官衰竭和死亡至关重要.
研究的目的:
- 为了阐明阿马托克辛诱导的肝损伤的分子机制.
- 建立针对性治疗干预的理论框架.
- 为了确定肝细胞中阿马托克辛的关键分子标.
主要方法:
- 计算毒理学 (ProTox-3.0,ADMETlab 2.0) 用于毒理学分析.
- 使用STITCH和SwissTargetPrediction数据库进行目标预测.
- 生物信息学分析包括PPI网络,GO和KEGG路径丰富.
- 分子对接模拟以评估结合亲缘关系.
主要成果:
- 确定了11个潜在的阿马托克辛标和1,730个与肝损伤相关的基因.
- 确定SP1和CNR1作为阿马托克辛诱导的肝损伤的共识分子标.
- 通过分子对接,证明了阿马托克辛与SP1和CNR1的高亲缘关系结合.
- 功能性丰富分析揭示了被破坏的生物过程和信号通路.
结论:
- 亚马托克辛通过直接结合SP1和CNR1.1诱导肝毒性.
- 这种结合会扰乱下游的转录调节和信号级联.
- 确定的目标为开发针对性治疗对抗阿马托克辛中毒提供了基础.
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