O'Toole S J, Sharma A, Karamanoukian H L, Holm B, Azizkhan R G, Glick P L
Buffalo Institute of Fetal Therapy (BIFT), NY, USA.
J Pediatr Surg. 1996 Apr;31(4):546-50. doi: 10.1016/s0022-3468(96)90493-5.
Experimental tracheal ligation (CDH + TL) has been shown to reverse the profound lung hypoplasia associated with congenital diaphragmatic hernia (CDH) and to normalize gas exchange. The aim of this study was to determine whether this experimental therapy would correct the surfactant deficiency present in the fetal lamb model of CDH.
The CDH lamb model was created at 80 days' gestation, and tracheal ligation was performed at 110 days. At term, the lambs were delivered and were ventilated for 30 minutes. The lambs were killed, a pressure-volume curve performed, and the lungs lavaged to measure total phospholipid content. Finally, type II pneumocytes were isolated, and surfactant synthesis was assessed by the incorporation of tritiated choline into phosphatidylcholine.
CDH + TL resulted in a lung significantly larger than that of CDH alone. The lungs of the former also had better oxygenation and ventilation. However, lung compliance was reduced compared with controls. Total alveolar phospholipid was dramatically lower, with a decrease in the proportion of phosphatidylcholine present. Surfactant synthesis by the isolated type II pneumocyte was significantly impaired.
Occlusion of the fetal trachea produces a lung comparable in size to a normal control lung. However, broncheoalveolar lavage analysis shows a marked reduction in total phospholipid, with a decrease in surfactant synthesis by the type II pneumocyte. The normalization of gas exchange reported for this animal model may be only a transient phenomenon. Further studies are required to assess the impact of this surfactant deficiency on long-term lung function.
实验性气管结扎术（先天性膈疝+气管结扎）已被证明可逆转与先天性膈疝（CDH）相关的严重肺发育不全，并使气体交换正常化。本研究的目的是确定这种实验性治疗是否能纠正CDH胎羊模型中存在的表面活性剂缺乏。
在妊娠80天时建立CDH胎羊模型，并在110天时进行气管结扎。足月时，将羔羊分娩并通气30分钟。处死羔羊，进行压力-容积曲线测定，并对肺进行灌洗以测量总磷脂含量。最后，分离II型肺细胞，并通过将氚标记的胆碱掺入磷脂酰胆碱中来评估表面活性剂的合成。
先天性膈疝+气管结扎导致的肺明显大于单纯先天性膈疝的肺。前者的肺也具有更好的氧合和通气。然而，与对照组相比，肺顺应性降低。总肺泡磷脂显著降低，磷脂酰胆碱所占比例下降。分离的II型肺细胞合成表面活性剂的能力明显受损。
胎儿气管闭塞产生的肺大小与正常对照肺相当。然而，支气管肺泡灌洗分析显示总磷脂显著减少，II型肺细胞合成表面活性剂的能力下降。该动物模型中报道的气体交换正常化可能只是一种短暂现象。需要进一步研究来评估这种表面活性剂缺乏对长期肺功能的影响。
