通过促进核因子红色素2相关因子2的表达来抑制铁亡,激活酸受体可缓解毒症
Hongxuan Liu1, Meixia Yang2, Zhiyong Zhao2
1Institute of Disaster and Emergency Medicine, Tianjin University, Tianjin, 300072, China; Department of Emergency Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.
The American journal of the medical sciences
|August 21, 2025
概括
通过增强NRF2通路,降低铁亡,并提供新的治疗策略,激活酸碳受体 (AhR) 能够防止败血症引起的急性损伤 (AKI).
科学领域:
- 肝脏病学
- 分子生物学
- 毒理学
背景情况:
- 败血症引起的急性损伤 (AKI) 构成了全球重大健康挑战.
- 炎症和管细胞损伤是AKI发病的关键因素.
- 酸受体 (AhR) 可能减轻AKI,但其机制需要阐明.
研究的目的:
- 调查AhR激活对败血症诱导的AKI的保护机制.
- 探索 AhR 在调节 AKI 的细胞通路中的作用.
- 确定AKI治疗的潜在治疗点.
主要方法:
- 在体内和体外使用脂聚糖 (LPS) 建立了败血症诱导的AKI模型.
- 蛋白质表达是通过西部抹杀进行评估的.
- 组织学染色评估了组织损伤,并量化了特定的分子标记.
主要成果:
- 用6 - 甲基醇[3,2-b]碳醇 (FICZ) 激活AhR显著减弱了LPS诱导的AKI并减少了细胞死亡.
- FICZ治疗降低了氧化应激标志物 (MDA,4-HNE,Fe2+) 和增加了抗氧化酶 (GPX4,SLC7A11).
- FICZ促进了AhR和NRF2的核转移,抑制了细胞铁亡.
结论:
- 通过增强的NRF2核转位和表达,AhR激活可对GPX4和SLC7A11进行上调.
- 这一过程减轻了脂质过氧化物积累和铁,为AKI提供了一种新的治疗方法.
- 这些发现强调AhR是AKI和未来转化研究的潜在治疗目标.
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