Nardo L, Maritz G, Harding R, Hooper S B
Department of Physiology, Monash University, Clayton, Victoria, Australia.
Exp Lung Res. 2000 Mar;26(2):105-19. doi: 10.1080/019021400269907.
Increased expansion of the fetal lung, caused by obstruction of the fetal trachea, is a potent stimulus for growth and structural development of the fetal lung. Our aim was to analyze the changes in lung structure induced by fetal tracheal obstruction and to identify cell types that contribute to the growth response. Fetal sheep were exposed to 2, 4, or 10 days of tracheal obstruction (TO) and on day 128 of gestation (term "147 d"), were injected with 3H-thymidine 8 hours before tissues were collected. The right lung was fixed at 20 cm H2O and prepared for stereological and autoradiographic analysis. Alveolar wall thickness (7.8 +/- 0.3 microns vs 5.5 +/- 0.4 microns) and percent tissue space (27.9 +/- 0.9% vs 21.4 +/- 2.8%) were increased at 2 days of TO, but were not different from control at 4 and 10 days. The luminal surface area of the right lung increased gradually from 2.4 +/- 0.2 m2/kg in control fetuses to 3.6 +/- 0.4 m2/kg following 10 days of TO and this increase was accompanied by an increase in alveolar number (control: 808 x 10(6) +/- 81.9 x 10(6) vs 10d obstruct: 1254 x 10(6) +/- 63 x 10(6). Alveolar diameter increased at 2 days of TO (51.8 +/- 1.4 microns vs 43.8 +/- 1.9 microns), but was not increased further at 4 or 10 days. The percentage of dividing cells was increased at 2 days of TO (12.64 +/- 3.39% vs 1.73 +/- 0.31%), remained elevated at 4 days (5.01 +/- 0.27%), but had returned to control by day 10. The increase at 2 days was due to division of type II epithelial cells, fibroblasts, and endothelial cells. We conclude that increased expansion of the fetal lung induces time-dependent changes in lung structure and cell division rates; these include a transient increase in alveolar wall thickness, a rapid increase in alveolar number, and a gradual increase in luminal surface area. The latter is probably caused by an increase in alveolar number rather than an increase in the alveolar size.
胎儿气管阻塞导致的胎儿肺扩张增加，是胎儿肺生长和结构发育的有力刺激因素。我们的目的是分析胎儿气管阻塞引起的肺结构变化，并确定促成生长反应的细胞类型。将胎羊暴露于2、4或10天的气管阻塞（TO），在妊娠第128天（足月“147天”），在收集组织前8小时注射3H-胸腺嘧啶核苷。右肺在20 cm H2O压力下固定，准备进行体视学和放射自显影分析。气管阻塞2天时，肺泡壁厚度（7.8±0.3微米对5.5±0.4微米）和组织间隙百分比（27.9±0.9%对21.4±2.8%）增加，但在4天和10天时与对照组无差异。右肺管腔表面积从对照胎儿的2.4±0.2平方米/千克逐渐增加到气管阻塞10天后的3.6±0.4平方米/千克，这种增加伴随着肺泡数量的增加（对照：808×10⁶±81.9×10⁶对阻塞10天：1254×10⁶±63×10⁶）。气管阻塞2天时肺泡直径增加（51.8±1.4微米对43.8±1.9微米），但在4天或10天时未进一步增加。气管阻塞2天时分裂细胞百分比增加（12.64±3.39%对1.73±0.31%），4天时仍升高（5.01±0.27%），但到第10天已恢复到对照水平。2天时的增加是由于II型上皮细胞、成纤维细胞和内皮细胞的分裂。我们得出结论，胎儿肺扩张增加会引起肺结构和细胞分裂率的时间依赖性变化；这些变化包括肺泡壁厚度的短暂增加、肺泡数量的快速增加以及管腔表面积的逐渐增加。后者可能是由于肺泡数量增加而非肺泡大小增加所致。
