BIOCHEMISTRY OF PULMONARY SURFACTANT AND INFLAMMATION

(改编自申请人的摘要) 呼吸窘迫综合征的例子是炎症、表面活性剂功能的丧失和肺泡塌陷。结合这些特征的成年兔子模型将用于评估实验性治疗方法。该方法涉及用稀释的表面活性剂灌洗，以去除炎症渗出物，恢复肺功能并防止炎症复发。拟议的研究将与平行临床试验（IND 46,164）交叉，其中稀释的KL4-表面活性剂将用作ARDS患者的灌洗剂。在目前的项目中，成年兔子在去除内在表面活性剂并气管内滴注 LPS 或吸入稀 HC1 后会出现肺损伤。由此产生的发炎的肺不张肺将接受表面活性剂的治疗，通过推注或用稀释的表面活性剂或作为对照的盐水灌洗来给予。研究重点：（1）清除肺部渗出物，改善肺功能，抑制炎症复发； (2)在肺泡微环境中给药时肺泡扩张的稳定性以及特异性抑制炎症介质对肺损伤的作用； (4)IL-8在肺部炎症发生发展中的作用。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.