Airway Surface Dehydration Aggravates Cigarette Smoke-Induced Hallmarks of COPD in Mice

Introduction
Airway surface dehydration, caused by an imbalance between secretion and absorption of ions and fluid across the epithelium and/or increased epithelial mucin secretion, impairs mucociliary clearance. Recent evidence suggests that this mechanism may be implicated in chronic obstructive pulmonary disease (COPD). However, the role of airway surface dehydration in the pathogenesis of cigarette smoke (CS)-induced COPD remains unknown.
Objective
We aimed to investigate in vivo the effect of airway surface dehydration on several CS-induced hallmarks of COPD in mice with airway-specific overexpression of the β-subunit of the epithelial Na+ channel (βENaC).
Methods
βENaC-Tg mice and wild-type (WT) littermates were exposed to air or CS for 4 or 8 weeks. Pathological hallmarks of COPD, including goblet cell metaplasia, mucin expression, pulmonary inflammation, lymphoid follicles, emphysema and airway wall remodelling were determined and lung function was measured.
Results
Airway surface dehydration in βENaC-Tg mice aggravated CS-induced airway inflammation, mucin expression and destruction of alveolar walls and accelerated the formation of pulmonary lymphoid follicles. Moreover, lung function measurements demonstrated an increased compliance and total lung capacity and a lower resistance and hysteresis in βENaC-Tg mice, compared to WT mice. CS exposure further altered lung function measurements.
Conclusions
We conclude that airway surface dehydration is a risk factor that aggravates CS-induced hallmarks of COPD.

引言
气道表面脱水由上皮离子与液体的分泌-吸收失衡和/或上皮黏蛋白分泌增加引发，会损害黏液纤毛清除功能。现有研究证据表明，该机制可能与慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）相关，但气道表面脱水在香烟烟雾（cigarette smoke, CS）诱导的COPD发病机制中的作用仍未明确。

研究目的
本研究旨在通过气道特异性过表达上皮钠通道β亚基（βENaC）的小鼠模型，在体探究气道表面脱水对香烟烟雾诱导的多项COPD特征性病理改变的影响。

研究方法
将βENaC转基因（Tg）小鼠与野生型（wild-type, WT）同窝仔鼠分别暴露于空气或香烟烟雾中，持续4周或8周。检测各组小鼠的COPD特征性病理改变，包括杯状细胞化生、黏蛋白表达、肺部炎症、淋巴滤泡形成、肺气肿及气道壁重构，并测定其肺功能。

研究结果
βENaC-Tg小鼠的气道表面脱水可加重香烟烟雾诱导的气道炎症、黏蛋白表达及肺泡壁破坏，并加速肺部淋巴滤泡的形成。与野生型小鼠相比，βENaC-Tg小鼠的肺功能检测显示其顺应性与肺总量升高，而气道阻力与滞后性降低；香烟烟雾暴露进一步改变了肺功能相关指标。

研究结论
本研究证实，气道表面脱水是加重香烟烟雾诱导的COPD特征性病理改变的危险因素。