Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Respirology. 2013 Aug;18(6):978-82. doi: 10.1111/resp.12114.
Alveolar fluid clearance (AFC) is important for the resolution of acute lung injury (ALI). The role of cystic fibrosis transmembrane conductance regulator (CFTR) in AFC has not been entirely elucidated in animal models of ALI. The aim of this study was to investigate the role of CFTR and its mechanisms in AFC in normal and ALI mice.
Seventy mice were randomly divided into 14 groups and ALI was established by intratracheal instillation of lipopolysaccharide (LPS). After 48 h, CFTR activator CFTRact-16 or inhibitor CFinh-172 with or without β-agonist was instillated intratracheally and AFC was measured with radioisotopic tracer.
Although there was no effects of CFTRact-16 on AFC in mice with or without isoproterenol, CFinh-172 markedly decreased isoproterenol-stimulated AFC in both normal (P < 0.01) and LPS-induced ALI mice (P < 0.01) and there was significantly decreased basal AFC in ALI mice (P < 0.05).
These results provide direct functional evidence for CFTR in cAMP-mediated AFC in both normal and ALI mice.
肺泡液清除（AFC）对于急性肺损伤（ALI）的恢复至关重要。囊性纤维化跨膜电导调节因子（CFTR）在 ALI 动物模型中的 AFC 中的作用尚未完全阐明。本研究旨在探讨 CFTR 及其在正常和 ALI 小鼠 AFC 中的作用机制。
70 只小鼠随机分为 14 组，通过气管内滴注脂多糖（LPS）建立 ALI 模型。48 小时后，气管内滴注 CFTR 激活剂 CFTRact-16 或抑制剂 CFinh-172，并联合或不联合β-激动剂，用放射性示踪剂测量 AFC。
虽然 CFTRact-16 对异丙肾上腺素刺激的 AFC 没有影响，但 CFinh-172 明显降低了正常（P<0.01）和 LPS 诱导的 ALI 小鼠（P<0.01）中异丙肾上腺素刺激的 AFC，并且 ALI 小鼠的基础 AFC 明显降低（P<0.05）。
这些结果为 CFTR 在正常和 ALI 小鼠中 cAMP 介导的 AFC 中的作用提供了直接的功能证据。
