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上腺素受体亚型有差异地影响阿克罗林诱导的呼吸系统,血管泄漏和炎症反应
Devin I Alewel1, Stephen H Gavett2, Katherine M Rentschler3
1Existing Chemicals Risk Assessment Division, Office of Chemical Safety and Pollution Prevention, U.S. Environmental Protection Agency, Research Triangle Park, NC, United States of America.
Toxicology and applied pharmacology
|March 18, 2025
概括
上腺素受体 (AR) 影响呼吸系统对烯暴露的反应. 阻断α-AR亚型会加重呼吸问题,而β-AR阻断剂可以提供一些保护,防止炎症和来自空气污染物的血管泄漏.
科学领域:
- 环境毒理学环境毒理学
- 呼吸系统药理学 呼吸系统药理学
- 上腺体受体信号传递
背景情况:
- 上腺素受体 (AR) 对心血管和肺功能至关重要.
- AR亚型在空气污染物引起的呼吸系统损伤中的具体作用尚不清楚.
- 阿克罗莱因是一种常见的空气污染物,具有已知的呼吸系统刺激性.
研究的目的:
- 调查特定上腺素受体亚型 (α1-AR,α2-AR,β-AR) 在阿克罗林诱导的呼吸系统影响中的贡献.
- 确定选择性AR抗剂如何调节呼吸,炎症和血管对烯暴露的反应.
主要方法:
- 维斯塔-京都大鼠每天接受9天的亚型特异性AR抗剂治疗:普拉佐辛 (α1-AR),约欣宾 (α2-AR) 或醇 (β-AR).
- 在第8天和第9天,老鼠每天暴露在空气或阿克罗莱因 (1.6或3.2 ppm) 中,每天4小时.
- 分析了呼吸功能 (整息图),支气管膜洗液 (BALF),鼻洗液 (NALF) 和血液参数.
主要成果:
- 暴露于阿克罗莱因会降低呼吸能力,这种效应在治疗普拉佐辛和约欣宾时会恶化.
- 在NALF和BALF中,阿克罗莱因诱导的中性和淋巴细胞炎症被普拉佐辛和约欣宾加剧,但被普罗兰罗尔减轻.
- 在NALF中,propranolol治疗减少了阿克罗莱因诱导的血管蛋白泄漏和炎症性细胞因子水平.
结论:
- 交感神经系统介导的上腺素受体信号传递显著影响了暴露于阿克罗莱因的呼吸系统健康影响.
- 特定的AR亚型差异调节呼吸,血液动力学和对空气污染物的炎症反应.
- 这些发现表明,接受上腺激素疗法的人可能会在暴露于空气污染时经历不同的呼吸道健康结果.
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