Boucher R C
Cystic Fibrosis/Pulmonary Research and Treatment Center, 7011 Thurston-Bowles Building, CB# 7248, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Adv Drug Deliv Rev. 2002 Dec 5;54(11):1359-71. doi: 10.1016/s0169-409x(02)00144-8.
The pathogenesis of cystic fibrosis (CF) lung disease is reviewed, focusing on an overview of the physiologic mechanisms that regulate mucus transport. A major emphasis is placed on the active transport systems that regulate the airway surface liquid (ASL) volume and, particularly, regulate the volume of the periciliary liquid (PCL) layer. A sequence is developed for CF whereby there is a depletion of the PCL that reflects the combined dysfunctions of accelerated Na(+)-dependent volume absorption and failure to secrete Cl(-). Both dysfunctions are a direct consequence of missing cystic fibrosis transmembrane conductance regulator (CFTR) at the apical membrane of airway epithelial cells. PCL depletion leads to failure of mucus transport, which is associated with persistent mucin secretion and formation of adherent mucus plaques and plugs. These plugs become the nidus for persistent bacterial airway infections that ultimately lead to a markedly anaerobic luminal environment.
本文综述了囊性纤维化（CF）肺部疾病的发病机制，重点概述了调节黏液转运的生理机制。主要强调了调节气道表面液体（ASL）量，特别是调节纤毛周围液体（PCL）层量的主动转运系统。针对CF建立了一个序列，即PCL耗竭，这反映了依赖Na⁺的加速容量吸收和Cl⁻分泌失败的联合功能障碍。这两种功能障碍都是气道上皮细胞顶端膜上缺失囊性纤维化跨膜传导调节因子（CFTR）的直接后果。PCL耗竭导致黏液转运失败，这与黏蛋白持续分泌以及黏附性黏液斑块和栓子的形成有关。这些栓子成为持续性细菌气道感染的病灶，最终导致明显的厌氧管腔环境。
