斯瓦烯环氧化酶通过内细胞网膜介导的铁灭菌促进了帕拉克瓦特诱导的肺毒性
Yanyan Zhu1, Wenwen Zhao1, Wan Li2
1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China.
Journal of advanced research
|June 3, 2025
概括
帕拉克瓦特除草剂会导致致命的肺损伤. 向 squalene epoxidase (SQLE) 与 liranaftate (LNT) 抑制铁亡和内分泌网膜应激,改善了小鼠模型中的生存率.
科学领域:
- 毒理学 毒理学 毒理学
- 生物化学 生化学
- 药理学 药理学是指药理学的学科.
背景情况:
- 帕拉克瓦特 (PQ) 是一种广泛使用的除草剂,会导致严重的肺损伤.
- 由于PQ引起的肺毒性的确切机制尚不清楚,并且缺乏有效的解毒剂.
- 铁和内细胞网膜 (ER) 压力与PQ毒性有关.
研究的目的:
- 调查烯环氧化酶 (SQLE) 在PQ诱导的铁和ER应激中的作用.
- 为了评估SQLE抑制剂liranaftate (LNT) 对PQ毒性的治疗潜力.
主要方法:
- 细胞活力测试 (CCK-8,ATP,PI染色) 用于评估细胞毒性.
- 流式细胞计量量化了性铁和脂质过氧化.
- 使用特定染料可视化ER和线粒体形态.
- 在体内研究中使用了PQ诱导的急性肺损伤 (ALI) 的小鼠模型.
主要成果:
- 通过依赖ER压力的PERK/eIF2α激活,PQ诱导铁,SQLE作为关键调解者.
- 通过减少可变铁,脂质过氧化和ER/线粒体损伤,LNT治疗减少了PQ诱导的细胞毒性.
- 在体内,LNT显著提高了从45%到95%的生存率,并减少了ALI的严重程度.
结论:
- 铁和SQLE在帕拉克瓦特毒性中起着关键作用.
- 抑制铁和向SQLE为PQ中毒提供了潜在的治疗策略.
- 利拉纳酸盐 (LNT) 显示出作为潜在的抗药物对帕拉奎特诱导的急性肺损伤的承诺.
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