作为氧化应激和脂质代谢障碍中分子毒理学机制的NRF2通路激活
Muhammad Arif Asghar1, Lie Yuan1, Yazhen Zhang1
1College of Pharmacy, Chongqing Medical University, Chongqing, PR China.
Journal of biochemical and molecular toxicology
|December 8, 2025
概括
核因子红色素2相关因子2 (NRF2) 途径调节抗氧化反应和脂质代谢. 激活NRF2可以通过减少有毒脂质积累和氧化损伤来治疗NAFLD等脂质疾病.
科学领域:
- 分子毒理学 分子毒理学
- 脂质代谢 脂质代谢是什么
- 氧化压力是一种氧化压力.
背景情况:
- 脂质代谢障碍与氧化应激和炎症有关,有助于NAFLD,动脉样硬化和代谢综合征.
- 该NRF2通路对于抗氧化剂防御和维持脂质平衡至关重要.
- 了解NRF2在脂质代谢中的作用是解决这些疾病的关键.
研究的目的:
- 在脂质代谢中研究NRF2途径的分子毒理学.
- 为了确定参与脂质相关慢性肝病的NRF2调节基因.
- 评估NRF2激活剂对脂质代谢障碍的治疗潜力.
主要方法:
- 对NRF2调节基因的GEO数据集的转录基因分析.
- 对NRF2激活剂对脂质毒性影响的临床元分析.
- 网络药理学绘制NRF2和脂质毒性目标的地图.
- 分子对接以评估NRF2激活器与KEAP1的结合.
主要成果:
- 3178个差异表达的基因将NRF2与氧化应激,铁亡和谷氨代谢联系起来.
- NRF2激活剂显著降低了甘油三 (21.81%),LDL (18.36%) 和总胆固醇 (14.15%).
- 网络药理学发现了985个重叠的基因; 奎尔素和黄素显示强烈的KEAP1结合.
结论:
- NRF2是氧化应激和脂质新陈代谢交叉点的中央调节者.
- NRF2激活剂减轻有毒脂质积累和氧化损伤.
- NRF2调节是NAFLD,动脉样硬化和代谢综合征的一种有前途的治疗策略.
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