Functional deficiency of pulmonary surfactant in the newborn infant

为阐明新生儿肺表面活性物质功能缺陷的病理生理机制，采用气管内注射内毒素的方法建立了新生仔猪急性呼吸窘迫综合征动物模型。在该动物模型中，消除了多器官衰竭，仅可获得类似于人类败血症引起的ARDS的肺病理。肺泡灌洗液(BAIF)表面活性降低、进行性低氧血症、高碳酸血症、肺顺应性降低、氧分压升高、弹力酶活性升高、过氧化脂质增多是肺病理改变的主要表现。通过尸检组织学检查证实肺组织病理改变，评价重组人超氧化物歧化酶(rh-SOD)预防和治疗对急性肺损伤的影响。气管内预防性给予rh-SOD对内毒素所致的肺损伤是有效的，可维持正常血氧和正常二氧化碳，维持肺顺应性，减少过氧化脂质的产生。组织学检查显示，经超氧化物歧化酶处理的动物肺损伤程度较轻，但在肺损伤形成后，气管内给予rh-SOD对肺损伤的改善作用不明显。

In order to elucidate the pathophysiology of functional deficiency of pulmonary surfactant in the newborn infants, an animal model of acute respiratory distress syndrome was produced in the newborn piglet by the administration of endotoxin (lipopolysaccharides : LPS) via trachea. In this animal model, multiple organ failure was eliminated and solely the lung pathology similar to human ARDS due to septicemia could be achieved. The lung pathology was confirmed by the decreased surface activity, progressive hypoxemia and hypercarbia, decreased lung compliance, increased O_2 productivity, increased elastase activity, and increased lipid peroxides in bronchoalveolar lavage fluid (BAIF). Lung pathology was confirmed also by histological examination on autopsy.Then, the effect of prophylactically and therapeutically administered recombinant human superoxide dismutase (rh-SOD) on acute lung injury was evaluated. The prophylactic intratracheal administration of rh- SOD for lung injury caused by endotoxin was effective, It was confirmed by the maintenance of normoxemia and normocapnia, and lung compliance, and decreased production of lipid peroxides. Histologic examination also showed that the degrees of lung injury were milder in SOD pretreated animals.However, after the formation of lung injury, the intratracheal administration of rh-SOD was no more effective on the improvement.