De Paepe M E, Papadakis K, Johnson B D, Luks F I
Rhode Island Hospital, Department of Pathology, Providence 02903, USA.
Virchows Arch. 1998 Jan;432(1):7-16. doi: 10.1007/s004280050128.
Tracheal occlusion in utero has been shown to cause accelerated fetal lung growth and is now being considered as a therapeutic modality for pulmonary hypoplasia. We report the effects of tracheal ligation on the surfactant-producing type II pneumocyte population. Three groups of fetal lambs underwent tracheal ligation of 2 weeks', 4 weeks' and 6 weeks' duration, respectively, and all were sacrificed at 136 days' gestation (9 days pre-term). Nonoperated twins served as controls. The type II pneumocyte population was studied morphometrically using a combination of anti-surfactant protein B immunohistochemistry and computer-assisted stereologic morphometry at light and electron microscopic levels. Single-factor ANOVA was used for statistical analysis. Two weeks of tracheal ligation resulted in doubling of the total lung volume as a result of airspace distension and, to lesser extent, growth of the tissue compartment. With increasing duration of tracheal ligation, there was no additional lung growth. However, more prolonged tracheal occlusion was found to result in significant reduction of the surfactant system, as reflected in the marked decrease of total pneumocyte type II volume (3.14 cm3, 0.95 cm3, and 0.46 cm3, after 2, 4, and 6 weeks of ligation, compared with 5.96 cm3 for controls) and total pneumocyte type II number (13.9 x 10(9), 3.8 x 10(9), and 2.4 x 10(9), compared with 53.2 x 10(9) for controls). Ultrastructural analysis of the type II cells in obstructed lungs showed vacuolar degenerative changes that, after 6 weeks of ligation, were apparently irreversible. In utero tracheal ligation causes fetal lung hyperplasia, but results in reduction of and injury to the surfactant-producing cell population. Before tracheal occlusion can find wide-spread clinical application, its pathophysiology needs to be further elucidated.
子宫内气管阻塞已被证明可导致胎儿肺加速生长，目前正被视为治疗肺发育不全的一种治疗方式。我们报告了气管结扎对产生表面活性剂的II型肺上皮细胞群体的影响。三组胎羊分别接受了持续2周、4周和6周的气管结扎，所有胎羊均在妊娠136天（早产9天）时处死。未手术的双胞胎作为对照。使用抗表面活性蛋白B免疫组织化学和计算机辅助立体形态计量学相结合的方法，在光镜和电镜水平上对II型肺上皮细胞群体进行形态计量学研究。采用单因素方差分析进行统计学分析。气管结扎2周导致肺总体积因气腔扩张而加倍，组织部分的生长程度较小。随着气管结扎时间的延长，肺没有进一步生长。然而，发现更长时间的气管阻塞会导致表面活性剂系统显著减少，这表现为II型肺上皮细胞总体积（结扎2周、4周和6周后分别为3.14 cm³、0.95 cm³和0.46 cm³，而对照组为5.96 cm³）和II型肺上皮细胞总数（分别为13.9×10⁹、3.8×10⁹和2.4×10⁹，而对照组为53.2×10⁹）明显减少。对阻塞肺中II型细胞的超微结构分析显示有空泡变性改变，结扎6周后这些改变显然是不可逆的。子宫内气管结扎可导致胎儿肺增生，但会导致产生表面活性剂的细胞群体减少和损伤。在气管阻塞能够广泛应用于临床之前，其病理生理学需要进一步阐明。
