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。这一反应包括涌入和 随着中性粒细胞的释放，中性粒细胞被隔离到肺中 中性粒细胞弹性蛋白酶等有毒介质。Eastase可能 切断和破坏弹性蛋白以及大分子，如 表面活性脱辅基蛋白。令人惊讶的是，几乎什么都不知道 关于表面活性物质功能障碍之间的函数关系 ARDS肺损伤修复过程中弹性蛋白的变化。 无论是受伤时弹性蛋白合成的状态还是 异常凝血素的存在影响对肺的整体反应 受伤情况尚不清楚。此外，虽然磷脂具有 抗炎作用，尚不清楚外源性有什么作用 会对减少炎症反应和影响 肺损伤后弹性蛋白损伤的研究。这个项目的总体目标是 因此，建议分析表面活性剂在 急性心肌梗死转基因小鼠模型中调节弹性蛋白合成的研究 由气管内给药造成的肺损伤 内毒素导入携带并活跃表达A基因的转基因小鼠 不同弹性蛋白基因突变的数量。新信息来自 这些研究可能有助于更好地理解这些因素 与ARDS的生存和康复相关，有无 肺部后遗症。他们还可以为更好的 对外源性肺表面活性物质治疗急性呼吸窘迫综合征的认识。

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.