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通过Connexin-hemichannels介导的ATP释放会在吸入后导致肺损伤
Ahmed Lazrak1, Zhihong Yu1, Sadis Matalon1
1Division of Molecular and Translational Biomedicine, Department of Anesthesiology and Perioperative Medicine, Pulmonary Injury and Repair Center, Heersinck School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States.
American journal of physiology. Cell physiology
|September 29, 2025
概括
吸入的气会通过改变膜蛋白和释放ATP而导致肺损伤. 早期治疗Gap27,一种连xin-hemichannel抑制剂,可以预防肺并保持肺功能.
科学领域:
- 毒理学 毒理学 毒理学
- 肺部医学 肺部医学
- 细胞生物学 细胞生物学
背景情况:
- 气 (Cl2) 的吸入会通过水解导致低和盐酸的肺损伤.
- 这些酸会改变膜蛋白,影响肺上皮层内液 (ELF) 功能.
- 连素 - 化学通道和ATP释放与诱导的肺损伤有关.
研究的目的:
- 研究气在ELF中对连xin-hemichannels和ATP释放的影响.
- 确定连xin-hemichannels 在诱导的肺和肺功能障碍中的作用.
- 评估Gap27,一种连xin-hemichannel抑制剂,作为一种潜在的治疗剂.
主要方法:
- 成年C57BL/6小鼠被暴露在400ppmCl2中30分钟.
- 在支气管支气管洗液 (BAL) 中测量ATP水平.
- 评估肺湿/干 (W/D) 比率和气膜液清除率 (AFC).
- 2型 (AT2) 细胞中ENaC和阴离子通道的电生理学记录.
- 暴露后使用Gap27及其影响的评估.
- 在人类呼吸道光滑肌细胞 (hASMCs) 中进行的试验涉及ATP和P2X7R抑制.
主要成果:
- 暴露于Cl2显著增加了BAL ATP水平,肺W/D比率,并降低了AFC.
- 电生理学揭示了ENaC和18 pS离子通道的开放概率降低.
- Gap27治疗恢复了ATP水平,使W/D比率和AFC正常化,并恢复了ENaC功能.
- Gap27还使呼吸道阻力在甲醇后的挑战中正常化.
- 在hASMC中引起的ATP反应,部分由P2X7R抑制剂逆转.
结论:
- 气通过促进连xin-hemichannel 开放和 ATP 释放来诱导肺损伤,从而导致肺.
- 使用Gap27的早期干预可以保持ENaC的功能,并防止胀的发展.
- 康尼克素-海米通道抑制是对气吸入伤害的有前途的治疗策略.
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