Benachi A, Delezoide A L, Chailley-Heu B, Preece M, Bourbon J R, Ryder T
Electron Microscopy Unit, Queen Charlotte's and Chelsea Hospital, London, United Kingdom.
Am J Respir Cell Mol Biol. 1999 Apr;20(4):805-12. doi: 10.1165/ajrcmb.20.4.3359.
In fetuses with diaphragmatic hernia (DH) lung development is impaired, and pulmonary hypoplasia is one of the main factors responsible for the poor outcome of the disease. A possible treatment consists of occluding trachea during lung development to retain pulmonary fluid and to force the lung to expand. Although it appeared promising at first, this technique has recently been reported to decrease type II cell number and to induce surfactant deficiency. The aim of this study was to investigate lung maturation further through ultrastructural examination in a fetal lamb model of DH created at 85 d, followed or not by endoscopic balloon tracheal occlusion (TO) at 120 d of gestation. The proportion of alveolar epithelial type I and type II cells was altered by both treatments: the type I/type II cell ratio, which was about 2 in control lungs, was decreased 4.5-fold in DH lungs but was increased 4.5-fold in DH+TO lungs. The proportion of undifferentiated cells was increased in DH lungs. Indeterminate cells sharing features of type II and type I cells that were not observed in controls were seldom seen in DH lungs and were numerous in DH+TO lungs. The number of lamellar bodies per type II cell was decreased in both DH and DH+TO groups. In DH lungs, wall structure presented an immature appearance, with cellular connective tissue and poor secondary septation of saccules. In DH+TO lungs, primary septa appeared more mature, with reduced connective tissue, but secondary septa were still buds, although elastin was present at their tips. A single capillary layer was found in all three groups (control, DH, and DH+TO) with no sign of septal capillary pairing. This first investigation in DH and DH+TO lungs through transmission electron microscopy thus enabled us to show that compression and forced expansion of the lung are both responsible for alterations in type II cell differentiation and septal development.
在患有膈疝（DH）的胎儿中，肺发育受损，肺发育不全是导致该疾病预后不良的主要因素之一。一种可能的治疗方法是在肺发育期间阻塞气管，以保留肺液并促使肺扩张。尽管该技术最初看起来很有前景，但最近有报道称，这种技术会减少II型细胞数量并导致表面活性剂缺乏。本研究的目的是通过超微结构检查，进一步研究在妊娠85天时建立的DH胎羊模型中肺的成熟情况，该模型在妊娠120天时是否接受内镜球囊气管阻塞（TO）。两种治疗方法均改变了肺泡I型和II型上皮细胞的比例：I型/II型细胞比例在对照肺中约为2，在DH肺中降低了4.5倍，但在DH+TO肺中增加了4.5倍。DH肺中未分化细胞的比例增加。在对照中未观察到的兼具II型和I型细胞特征的不确定细胞在DH肺中很少见，而在DH+TO肺中则很多。DH组和DH+TO组中每个II型细胞的板层小体数量均减少。在DH肺中，壁结构呈现不成熟的外观，有细胞性结缔组织且肺泡囊的次级分隔较差。在DH+TO肺中，初级隔看起来更成熟，结缔组织减少，但次级隔仍是芽状，尽管其尖端存在弹性蛋白。在所有三组（对照、DH和DH+TO）中均发现单一的毛细血管层，没有间隔毛细血管配对的迹象。因此，通过透射电子显微镜对DH和DH+TO肺进行的首次研究使我们能够表明，肺的压缩和强制扩张均导致II型细胞分化和间隔发育的改变。
