Relationship of airway epithelial ion transport to chronic bronchitis.
Relationship of airway epithelial ion transport to chronic bronchitis.
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DOI：
10.1513/pats.2306018
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Boucher, Richard C
中科院分区：
文献类型：
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作者：
Boucher, Richard C
不能正常清除粘液是慢性支气管炎（CB）发病机制中的一个关键事件。对于无法清除气道表面粘液的统一概念已经出现，其重点是异常高的黏液与气道表面液体体积比。在一定程度上，高黏液体积比与睫状体周液体层的丢失和黏液层粘附到细胞表面有关。黏液成为刺激和咳嗽的刺激物，是细菌感染的病灶。清除CB气道粘液的治疗方法应侧重于恢复粘蛋白和水的平衡。药物阻断上皮Na+通道，限制气道表面的体积吸收，是一种新的治疗靶点。在绵羊模型和人类受试者中进行的粘液清除研究表明，上皮Na+通道的阻断与粘液清除的加速有关，这表明上皮Na+通道的阻断可能确实是治疗CB的一种合理形式。
Failure to clear mucus normally is a critical event in the pathogenesis of chronic bronchitis (CB). A unifying concept for the failure to clear mucus from airway surfaces has emerged that focuses on an abnormally high mucin-to-airway surface liquid volume ratio. At a certain level, a high mucin-to-volume ratio is associated with loss of the periciliary liquid layer and adhesion of the mucus layer to the cell surface. Adherent mucus becomes a stimulus for irritation and cough and is the nidus for bacterial infection. Therapeutic approaches for clearing mucus from CB airways should focus on restoring the balance of mucin and water. Pharmacologic blockade of the epithelial Na+ channel, which is rate-limiting for volume absorption from airway surfaces, constitutes a novel therapeutic target. Studies of mucus clearance both in sheep models and human subjects demonstrate that blockade of the epithelial Na+ channel is associated with an acceleration of mucus clearance, suggesting that epithelial Na+ channel blockade may indeed constitute a rational form of therapy for CB.