ADMIN FOR MOLEC ENDOCRINOLOGY, RETROVIROLOGY & NATIVE HAWAII HLTH RES ACTIVITIES

急性呼吸窘迫综合征（ARDS）是一种严重的疾病， 死亡率在50- 70%之间。它的特点是强烈的 炎症反应。 这种反应包括大量涌入， 中性粒细胞进入肺的隔离， 有害介质如中性粒细胞弹性蛋白酶。 弹性蛋白酶可能 切割和破坏弹性蛋白以及大分子， 表面活性剂脱辅基蛋白 令人惊讶的是，几乎什么都不知道 关于表面活性剂功能失调与 弹性蛋白在ARDS肺损伤和修复过程中的变化。 无论是受伤时的弹性蛋白合成状态， clastin异常的存在影响了肺的整体反应 伤势不详。 此外，虽然磷脂具有 抗炎特性，目前尚不清楚外源性有什么作用 会减少炎症反应， 对肺损伤后弹性蛋白损伤的影响 这个项目的总体目标是 因此，建议分析表面活性剂的作用， 在急性炎症转基因小鼠模型中调节弹性蛋白合成 肺损伤，由细菌内给药造成 内毒素到携带并积极表达 不同弹性蛋白基因突变的数量。 提供的新情况 这些研究可能有助于更好地理解 与ARDS生存和恢复相关，有和没有 肺部后遗症 它们也可能有助于更好地 了解外源性表面活性物质在ARDS中的应用。

Acute respiratory distress syndrome (ARDS) is a serious disorder with a mortality rate between 50-70%. It is characterized by intense inflammatory response. This response consists of an influx and sequestration of neutrophils into the lung with the release of noxious mediators such as neutrophil elastase. EIastase may cleave and destroy elastin as well as macromolecules such as surfactant apoproteins. Surprisingly, almost nothing is known about the functional relationship between surfactant dysfiinction and changes in elastin in ARDS during lung injury and repair. Whether the status ofelastin synthesis at the time of the injury or the presence of abnormaI clastin affect the overall response to lung injury is unknown. Furthermore, while phospholipids possess anti-inflammatory properties, it is unknown what effect exogenous would have on reducing the inflammatory response and the effect on elastin damage after lung injury. The overall goal of this proposal therefore is to analyze the role of surfactants in modulating elastin synthesis in a transgenic mouse model of acute lung injury, created by the intratracheal administration of bacterial endotoxin into transgenic mice harboring and actively expressing a number of different elastin gene mutations. New information from these studies may contribute to a better understanding of factors related to ARDS survival and recovery, with and without pulmonary sequelae. They may also contribute to a better understanding of the use of exogenous surfactant therapy in ARDS.