Nardo L, Hooper S B, Harding R
Department of Physiology, Monash University, Clayton, Victoria, Australia.
Pediatr Res. 1998 Feb;43(2):184-90. doi: 10.1203/00006450-199802000-00005.
Obstruction of the fetal trachea causes liquid to accumulate within the future airways, which is a potent stimulus for lung growth. Our aim was to determine the relationship between the increase in fetal lung growth after tracheal obstruction and the increases in lung liquid volume and tracheal pressure to better understand the mechanisms involved in the growth response. The effects of 4 and 10 d of tracheal obstruction on lung DNA and protein contents and DNA synthesis rates were determined; these data were combined with data collected previously after 2 and 7 d of tracheal obstruction. Fetal lung liquid volumes and secretion rates were measured before (d 0) and on d 1, 2, 4, 7, and 10 after tracheal obstruction; fetal tracheal pressures were monitored throughout this period. Tracheal pressures increased from 2.9 +/- 0.8 mm Hg (control) to 4.3 +/- 0.4 mm Hg within 1 d of tracheal obstruction and remained at this elevated level for the duration of the obstruction period. Lung liquid volume increased progressively from 24.7 +/- 1.1 mL/kg on d 0 to 97.3 +/- 15.2 mL/kg at d 7 of tracheal obstruction, but had not increased further by d 10. Tracheal obstruction significantly increased lung DNA and protein contents above control values; over the 10-d period the increase in lung DNA content was closely related (r = 0.99) to the increase in lung liquid volume, but not to the increase in tracheal pressure. DNA synthesis rates were increased at 4 d of tracheal obstruction (by 66%) but had returned to control levels by d 10. We conclude that: 1) the mechanisms responsible for the acceleration in lung growth induced by tracheal obstruction are most active on d 2, remain active at a reduced level on d 4 and 7, and have returned to control levels by d 10; and 2) the increase in lung DNA content during tracheal obstruction (d 2-7) is closely related to the increase in lung liquid volume, but not to the increase in intraluminal pressure. Thus, we suggest that an increase in lung expansion is one of the primary factors responsible for the acceleration in fetal lung growth induced by tracheal obstruction.
胎儿气管梗阻会导致液体在未来的气道内积聚，这是肺生长的一个强大刺激因素。我们的目的是确定气管梗阻后胎儿肺生长增加与肺液体积和气管压力增加之间的关系，以便更好地理解生长反应所涉及的机制。测定了气管梗阻4天和10天对肺DNA和蛋白质含量以及DNA合成速率的影响；这些数据与先前在气管梗阻2天和7天后收集的数据相结合。在气管梗阻前（第0天）以及梗阻后第1、2、4、7和10天测量胎儿肺液体积和分泌速率；在此期间全程监测胎儿气管压力。气管压力在气管梗阻1天内从2.9±0.8毫米汞柱（对照）升至4.3±0.4毫米汞柱，并在梗阻期持续保持在这一升高水平。肺液体积从第0天的24.7±1.1毫升/千克逐渐增加至气管梗阻第7天的97.3±15.2毫升/千克，但到第10天未进一步增加。气管梗阻使肺DNA和蛋白质含量显著高于对照值；在10天期间，肺DNA含量的增加与肺液体积的增加密切相关（r = 0.99），但与气管压力的增加无关。气管梗阻4天时DNA合成速率增加（增加66%），但到第10天已恢复至对照水平。我们得出结论：1）气管梗阻诱导肺生长加速的机制在第2天最为活跃，在第4天和第7天以较低水平保持活跃，到第10天已恢复至对照水平；2）气管梗阻期间（第2 - 7天）肺DNA含量的增加与肺液体积的增加密切相关，但与管腔内压力的增加无关。因此，我们认为肺扩张增加是气管梗阻诱导胎儿肺生长加速的主要因素之一。
