臭氧诱导的肺损伤通过小鼠的PPAR介导的铁死作用
Juan Li1, Huai Wei1, Ning Wang1
1International Collaborative Laboratory for Air Pollution Health Effects and Intervention, School of Public Health, Xinxiang Medical University, 601 Jinsui Avenue, Xinxiang, 453003, Henan Province, China.
Biological trace element research
|October 6, 2024
概括
臭氧暴露会通过PPAR信号通路破坏脂质代谢,从而损害肺部,导致铁亡. 这项研究确定了臭氧引起的肺损伤背后的关键分子机制.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 臭氧水平的上升构成了严重的呼吸系统健康风险.
- 臭氧引起的肺损伤的分子机制尚未完全理解.
- 颗粒物 (PM2.5) 度已经下降,而臭氧污染在中国正在增加.
研究的目的:
- 研究臭氧引起的肺损伤的分子机制和潜在生物标志物.
- 分析新疆市 (2015-2022) 的臭氧污染数据.
- 为建立臭氧诱导的肺损伤小鼠模型.
主要方法:
- 臭氧污染数据分析.
- 臭氧诱导的肺损伤小鼠模型 (1ppm O3,4小时/天33天).
- 组织学分析 (HE染色) 和肺组织的高通量转录组测序.
主要成果:
- 臭氧暴露导致严重的肺损伤,包括炎症细胞透和膜损伤.
- 转录组分析确定了145个差异表达的基因,这些基因在PPAR信号通路和ferroptosis中得到了丰富.
- 在PPAR信号传递中的关键基因 (Adipoq,Lpl,Pck1,Plin1) 和与铁化相关的基因 (Acsl6,Scl7a11) 被下调.
结论:
- 臭氧暴露通过降低PPAR通路相关基因的调节来破坏脂质代谢.
- 这种干扰促进了肺细胞铁亡,加剧了臭氧引起的肺损伤.
- PPAR信号通路和铁亡是臭氧毒性的关键机制.
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