Carter E P, Umenishi F, Matthay M A, Verkman A S
Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California 94143, USA.
J Clin Invest. 1997 Sep 1;100(5):1071-8. doi: 10.1172/JCI119617.
Lung fluid is reabsorbed rapidly at birth to permit alveolar respiration. We reported previously that expression of aquaporins (AQP) 1, 4, and 5 in rat lung increased just after birth. The hypothesis was tested that the increased AQP expression is associated with increased osmotic water permeability (Pf) between the airspace and capillary compartments. Pf was measured in isolated perfused fetal and newborn rabbit lungs using a pleural surface fluorescence method (Carter, E.P., M.A. Matthay, J. Farinas, and A.S. Verkman. 1996. J. Gen. Physiol. 108:133-142). In response to perfusate osmolality increase from 300 to 600 mosM, initial rates of osmotic equilibration were 1.13+/-0.13 mosM/s at 0-12 h after birth, increasing to 1.52+/-0.19 mosM/s at 12-24 h, and 1.83+/-0.10 mosM/s at 24-84 h. Corresponding Pf values (in cm/s x 10(-2)), computed from d[mosM]/dt and alveolar surface-to-volume ratios, were 1.03+/-0.11 (0-12 h), 1.51+/-0.16 (12-24 h), and 1.88+/-0.09 (24-84 h). Pf was relatively low in prenatal (1.22-1.27, fetal days 29 and 31) and adolescent (1.25+/-0.08, 21-d) rabbit lungs. To test for involvement of molecular water channels, measurements were made of Arrhenius activation energy (Ea), mercurial inhibition, diffusional water permeability (Pd), and AQP expression. Temperature-dependence measurements showed a 25% decrease in Ea for Pf in lungs < 1 d vs. 4 d. Pf was decreased 30% by 0.5 mM HgCl2 in < 1-d lungs and 44% in 4-d lungs. Pd was 1.0 x 10(-)5 cm/s and did not change when Pf was increased by 75%. RNase protection assay showed increased transcript expression in the first 24 h after birth for rabbit isoforms of AQP1 and AQP4. These results provide the first functional data on water permeability in perinatal lung. The increased water permeability after birth may facilitate the maintenance of dry alveoli.
出生时肺内液体迅速重吸收以允许肺泡呼吸。我们之前报道过，出生后大鼠肺中水通道蛋白（AQP）1、4和5的表达增加。本研究检验了一个假设，即AQP表达增加与气腔和毛细血管腔之间渗透水通透性（Pf）增加有关。使用胸膜表面荧光法（Carter, E.P., M.A. Matthay, J. Farinas, and A.S. Verkman. 1996. J. Gen. Physiol. 108:133 - 142）在分离灌注的胎儿和新生兔肺中测量Pf。随着灌注液渗透压从300 mosM增加到600 mosM，出生后0 - 12小时的初始渗透平衡速率为1.13±0.13 mosM/s，12 - 24小时增加到1.52±0.19 mosM/s，24 - 84小时增加到1.83±0.10 mosM/s。根据d[mosM]/dt和肺泡表面积与体积比计算出的相应Pf值（单位：cm/s×10⁻²）分别为1.03±0.11（0 - 12小时）、1.51±0.16（12 - 24小时）和1.88±0.09（24 - 84小时）。Pf在产前（胎儿期第29天和31天，分别为1.22 - 1.27）和青春期（21日龄，1.25±0.08）兔肺中相对较低。为了检测分子水通道的参与情况，测量了阿累尼乌斯活化能（Ea）、汞抑制、扩散水通透性（Pd）和AQP表达。温度依赖性测量显示，与4日龄相比，<1日龄肺中Pf的Ea降低了25%。在<1日龄肺中，0.5 mM HgCl₂使Pf降低30%，在4日龄肺中降低44%。Pd为1.0×10⁻⁵ cm/s，当Pf增加75%时Pd不变。核糖核酸酶保护分析显示，出生后最初24小时内兔AQP1和AQP4同工型的转录本表达增加。这些结果提供了围产期肺水通透性的首个功能数据。出生后水通透性增加可能有助于维持肺泡干燥。
