在CEES诱导的肺损伤中,由NOX4/PPARγ轴介导的氧化-炎症交叉驱动的促炎性巨细胞两极化
Meng Cao1, Zhen Wang1, Hao Wu1
1School of Military Preventive Medicine, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Fourth Military Medical University, Xi'an 710032, China.
International immunopharmacology
|October 24, 2025
概括
暴露在硫中会通过NOX4和PPARγ信号传递破坏巨细胞平衡,从而导致肺损伤,从而整合了氧化应激和炎症. 这揭示了化学战剂保护的治疗目标.
科学领域:
- 毒理学 毒理学 毒理学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 硫 (SM) 是一种水性化学战剂,通过不明确的机制引起急性肺损伤.
- 氧化应激和炎症与SM诱导的肺损伤有关.
研究的目的:
- 为了研究氧化应激和炎症途径在硫类似物 (CEES) 中介的肺损伤中的作用.
- 在CEES引起的肺损伤中识别关键分子调节剂,特别是NOX4和PPARγ.
主要方法:
- 一个暴露于气溶CEES的小鼠模型和一个体外巨模型.
- 评估包括肺功能测试,转录组测序,RT-qPCR,西斑和ELISA.
- 功能验证使用药理学PPARγ激活和NOX4抑制.
主要成果:
- 暴露于CEES引起了气道阻塞,膜损伤和促炎性巨细胞的透.
- CEES上调NOX4和下调PPARγ,增加氧化应激 (ROS,MDA) 和炎症标志物 (TNF-α,IL-6).
- PPARγ激活促进了抗炎性标记物,而NOX4抑制减少了氧化应激,并将巨细胞转移到抗炎M2表型.
结论:
- 通过NOX4/PPARγ轴,CEES诱导巨细胞极化失衡,整合氧化应激和炎症以加剧肺损伤.
- 向NOX4/PPARγ通路为硫所引起的肺损伤提供了潜在的双重作用治疗策略.
- 这些发现对于开发针对化学战剂的对策具有重要意义.
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