NR1D1减轻了IL-17a诱导的小气道重塑在生物质烟雾诱导的COPD中
Lizhi Huang1, Juan Xu2, Hongbin Zhou3
1Department of Thoracic Surgery, the Peoples's Hospital of Baoan Shenzhen, Shenzhen, China.
Toxicology letters
|May 9, 2025
概括
生物质烟雾暴露会导致肺气和小呼吸道疾病. 降低NR1D1的调节会使IL-17a驱动的气道改造恶化,这表明COPD的潜在治疗点.
科学领域:
- 肺部医学 肺部医学
- 环境健康 环境健康
- 分子生物学分子生物学
背景情况:
- 生物质烟雾 (BS) 暴露是慢性阻塞性肺部疾病 (COPD) 的重要危险因素.
- 通过BS诱导小气道疾病的具体机制仍在调查中.
- 本研究的重点是介素-17a (IL-17a) 和核受体亚系1组D成员1 (NR1D1) 在BS诱导的肺病理中的作用.
研究的目的:
- 研究生物质烟雾引起的小气道疾病的机制.
- 探索IL-17a和NR1D1在与BS相关的COPD病变发生过程中的参与.
- 评估BS暴露,肺功能和呼吸道疾病标志物之间的相关性.
主要方法:
- 包括20名暴露于BS的慢性肺炎患者和13名对照患者,用高分辨率计算机断层扫描 (HRCT) 评估肺气和小呼吸道疾病.
- 测量了血清IL-17a水平,并使用了木烟诱导的COPD的小鼠模型.
- 在实验室中评估IL-17a和NR1D1对暴露于木烟颗粒物 (PM2.5) 的支气管上皮细胞 (BEAS-2b) 的 in vitro影响,使用流细胞计和西式涂抹.
主要成果:
- 与对照组相比,BS-COPD患者的肺气和小呼吸道疾病显著增加 (p < 0.01).
- 小呼吸道疾病与降低FEV1%的预测有很强的相关性 (r = -0.61,p = 0.004).
- 血清IL-17a水平与BS-COPD患者的小呼吸道疾病相关 (r = 0.48,p = 0.033),IL-17a促进了支气管上皮细胞的增殖,NR1D1下调放大了这种效应.
结论:
- 即使在非COPD患者中,生物质烟雾暴露也会导致肺气和小呼吸道疾病.
- NR1D1下调加剧了IL-17a介导的呼吸道重塑在体外.
- 这些发现表明,在BS引起的肺部疾病中,针对IL-17a/NR1D1通路的潜在治疗策略.
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