Hassett M J, Glick P L, Karamanoukian H L, Rossman J E, Wilcox D T, Azizkhan R G
Buffalo Institute of Fetal Therapy, Children's Hospital of Buffalo, State University of New York 14222, USA.
J Pediatr Surg. 1995 Aug;30(8):1191-4. doi: 10.1016/0022-3468(95)90019-5.
The pathophysiologic features of congenital diaphragmatic hernia (CDH) include pulmonary hypoplasia, pulmonary hypertension, surfactant deficiency, and decreased pulmonary compliance. When the surfactant deficiency is corrected using exogenous surfactant therapy, the pulmonary compliance improves, but does not reach normal values. Quasistatic saline pressure-volume measurements, which eliminate the air-liquid interface, confirm that CDH lungs are intrinsically less compliant than control lungs. The authors hypothesized that this abnormal lung compliance results from elevated concentrations of collagen and/or elastin in the lung. Therefore, they measured the collagen and elastin concentrations in CDH and control lung tissue. Also measured was the collagen concentration in the kidney, intestine, and dissected third-generation arterioles, venules, and bronchioles, to characterize further the pathology of CDH. The CDH model was created on the left side of fetuses in pregnant ewes at 80 days' gestation. The fetuses were delivered and killed at 140 days (full term, 145). The concentrations of collagen (as hydroxyproline), elastin, DNA, and total protein were measured using standard techniques. Although there was significantly more collagen per gram of lung tissue in the CDH lungs (1.334 mg/g v 0.885 mg/g in the controls) the elastin concentrations were not different. The elevated collagen concentration was not associated specifically with the conducting airways or vasculature. The collagen concentrations in CDH kidneys and intestines were the same as those of controls. The DNA/total protein ratios in the CDH and control lungs were identical. The results suggest that the elevated collagen concentration was present only in the lungs of CDH lambs, and that it was not attributable to atrophy or hypertrophy of the lungs. Thus, increased collagen in the lung parenchyma may be responsible for the intrinsic stiffness and decreased compliance of the CDH lungs.
先天性膈疝（CDH）的病理生理特征包括肺发育不全、肺动脉高压、表面活性物质缺乏以及肺顺应性降低。当使用外源性表面活性物质疗法纠正表面活性物质缺乏时，肺顺应性有所改善，但未达到正常值。消除气液界面的准静态盐水压力-容积测量证实，CDH患儿的肺本质上比对照肺的顺应性更低。作者推测这种异常的肺顺应性是由肺中胶原蛋白和/或弹性蛋白浓度升高所致。因此，他们测量了CDH和对照肺组织中的胶原蛋白和弹性蛋白浓度。还测量了肾脏、肠道以及解剖后的第三代小动脉、小静脉和细支气管中的胶原蛋白浓度，以进一步明确CDH的病理特征。在妊娠80天的孕羊胎儿左侧建立CDH模型。胎儿在140天（足月为145天）时娩出并处死。使用标准技术测量胶原蛋白（以羟脯氨酸计）、弹性蛋白、DNA和总蛋白的浓度。尽管CDH肺中每克肺组织的胶原蛋白含量明显更高（1.334 mg/g，而对照组为0.885 mg/g），但弹性蛋白浓度并无差异。胶原蛋白浓度升高并非与传导气道或脉管系统有特异性关联。CDH肾脏和肠道中的胶原蛋白浓度与对照组相同。CDH和对照肺中的DNA/总蛋白比值相同。结果表明，胶原蛋白浓度升高仅存在于CDH羔羊的肺中，且并非由肺萎缩或肥大所致。因此，肺实质中胶原蛋白增加可能是CDH肺固有硬度增加和顺应性降低的原因。
