人类暴露于柴油废气会诱导CYP1A1表达和AhR激活,而没有协调的抗氧化反应
M Friberg1, A F Behndig1, J A Bosson1
1Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
Particle and fibre toxicology
|December 7, 2023
概括
在人类中,柴油废气 (DE) 暴露会激活基碳化合物受体 (AhR) 和CYP1A1,但不会激活Nrf2介导的抗氧化防御. 这表明DE会引起炎症并改变排毒,而无需立即保护细胞.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 肺部医学 肺部医学
背景情况:
- 众所周知,柴油废气 (DE) 在人类中引起炎症.
- 德对内源性抗氧化剂和异生菌防御的影响尚不清楚.
- 核因子红色素2相关因子2 (Nrf2) 和酸受体 (AhR) 途径是这些防御的关键调节者.
研究的目的:
- 调查柴油废气暴露对人类呼吸道Nrf2和AhR激活的体内影响.
- 评估DE暴露后抗氧化剂和异生菌代谢酶的表达.
- 为了确定细胞抗氧化剂适应是否与DE诱导的炎症同时发生.
主要方法:
- 在一项双盲随机研究中,健康的受试者暴露在柴油废气 (DE) 或过空气中.
- 免疫组织化学用于检查支气管活检中Nrf2和AhR的核定位.
- 量化了CYP1A1,CYP1B1,阿尔多基因减少酶,环氧化酶和NQO1的表达.
主要成果:
- 暴露于DE会增加支气管中的中性粒细胞,淋巴细胞和乳腺细胞.
- 在DE暴露后的支气管上皮质中,AhR核转位和CYP1A1表达显著增加.
- Nrf2核转位没有增加,NQO1表达减少,表明没有诱导抗氧化防御.
结论:
- 人类暴露于柴油废气会急性诱导呼吸道中的AhR和第一阶段的异生物代谢 (CYP1A1).
- 这些反应发生在没有同时诱导Nrf2介导的抗氧化剂或II期异生菌防御的情况下.
- 与DE相关的化合物可能会引发炎症并改变排毒途径,而在人类呼吸道中没有立即的保护性细胞适应.
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