BIOCHEMISTRY OF PULMONARY SURFACTANT AND INFLAMMATION

呼吸窘迫综合症表现为炎症、表面活性物质功能丧失和肺泡塌陷。结合这些特征的成年兔模型将被用来评估一种实验性的治疗方法。该方法包括用稀释的表面活性物质冲洗以清除炎性渗出物，恢复肺功能和防止炎症复发，拟议的研究将与一项平行临床试验(IND 46,164)交叉进行，在该临床试验中，稀释的KL4-表面活性物质将用于ARDS患者的冲洗。在目前的项目中，成年兔在去除固有表面活性物质并在气管内注入脂多糖或吸入稀盐酸后会发生肺损伤。由此产生的发炎不电性肺将接受表面活性物质的治疗，给药方法是滴注表面活性物质，或用稀释的表面活性物质灌洗，或者作为对照，使用生理盐水。本研究的重点是：(1)清除肺渗出物，改善肺功能，抑制炎症复发；(2)肺泡扩张的稳定性及炎症介质在肺泡微环境中的特异性抑制对肺损伤的影响；(4)IL-8在肺部炎症发展中的作用。获得的数据将用于了解正在进行的临床试验的结果。

(Adapted from the Applicant's Abstract) Respiratory Distress Syndrome is exemplified by inflammation, loss of surfactant function and collapse of pulmonary alveoli. Models in adult rabbits that combine these features will be employed to assess an experimental method of treatment. The method involves lavaging with dilute surfactant to remove inflammatory exudate, restore pulmonary function and prevent recurrence of inflammation, The proposed studies will interdigitate with a parallel Clinical Trial (IND 46,164) in which dilute KL4-Surfactant will be used as a lavage in human beings with ARDS. In the current project adult rabbits will develop pulmonary injury after removal of intrinsic surfactant and intratracheal instillation of LPS or after aspiration of dilute HC1. The resulting inflamed ateelectatic lung will receive treatment with surfactant given by bolus instillation or by lavage with dilute surfactant, or, as control, saline. The study will focus on (1) removal of pulmonary exudate, improvement of pulmonary function and inhibition of recurrence of the inflammation; (2) stability of alveolar expansion and the effect of specific inhibition of inflammatory mediators on the pulmonary injury when administered in the alveolar microenvironment; (4) the role of IL-8 in the development of the pulmonary inflammation. The data obtained will be applied to understanding the results emerging from the ongoing Clinical Trial.