奎瑞通过调节KEAP1/NRF2/GPX4信号通路来抑制内皮细胞铁亡,缓解绝经后动脉样硬化
Ying Lv1,2,3, Xiuzhu Weng4,5, Yuxiao Zhu1,2,3
1Department of Cardiology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
British journal of pharmacology
|October 9, 2025
概括
奎尔素 (QCT) 通过通过KEAP1/NRF2通路预防细胞死亡,从而保护人免受绝经后动脉样硬化. 这项研究强调了QCT作为绝经后妇女动脉样硬化的潜在治疗方法.
科学领域:
- 心血管研究研究心血管研究
- 细胞生物学 细胞生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 绝经后的妇女面临加速动脉样硬化,原因是不太了解的机制.
- 在这种人群中,治疗动脉样硬化症的治疗选择有限.
研究的目的:
- 研究奎尔丁 (QCT) 对绝经后动脉样硬化的保护作用.
- 阐明涉及KEAP1/NRF2通路和内皮细胞铁亡的机制.
主要方法:
- 建立了一个绝经后动脉样硬化小鼠模型 (OVX + 高脂肪饮食).
- 通过组织学,生物化学和分子分析评估QCT和铁灭抑制剂 (Fer-1) 作用.
- 在体外使用ox-LDL诱导的内皮细胞研究了QCT的抗ferroptosis机制,并在体内和体外验证了NRF2的作用.
主要成果:
- 在OVX小鼠中,QCT和Fer-1显著降低了动脉样硬化标志物,包括脂质过氧化,铁沉积和内皮细胞铁.
- 在内皮细胞中,QCT上调了GPX4,下调了ACSL4和降低了ROS.
- QCT促进了KEAP1的降解,激活了NRF2和下游抗氧化途径,NRF2抑制减弱了效果.
结论:
- 奎尔素通过KEAP1无化介导的NRF2/GPX4通路激活来抑制内皮细胞铁亡,缓解绝经后动脉样硬化.
- 这些发现为绝经后动脉样硬化机制提供了新的见解.
- 建议QCT作为绝经后动脉样硬化症的潜在治疗剂.
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