TOXIC OXYGEN SPECIES MEDIATED ACUTE LUNG INJURY

这项提案的总体目标是研究 部分还原的氧物种介导了肺细胞损伤。主动脉和 肺动脉内皮细胞和II型肺泡上皮细胞 将被用作体外模型，因为这两个数据库都存在 这些细胞类型在体外和体内对氧化应激的反应。至 要做到这一点，提出的研究旨在阐明生化 氧化性肺损伤的机制。因此，以下具体目标将 收信人： 1.建立内皮细胞和II型肺泡上皮细胞 自由基致肺损伤研究的培养模型。 2.细胞质、膜和细胞外产生的游离 使用EPR技术的自由基。 3.将监测和调节细胞内自由基的形成 使用高氧和去偶联剂的电子传输。 4.利用自由基研究细胞内自由基的代谢 清除剂和脂质体介导的细胞内增强 抗氧化剂防御。 5.自由基损伤的细胞指数和损伤的调节 利用代谢指标和EPR测量研究结构 膜微域的变化。 这项研究方案代表了肺细胞生物学和 复杂的光谱方法用于鉴定 特异性自由基及其对膜结构的影响。 脂质体对抗氧化剂防御的药理作用 含有超氧化物歧化酶或过氧化氢酶会有潜在的好处 在许多新陈代谢的情况下。最后，完成上述具体工作 AIMS将提供对氧化性肺损伤的病因的洞察。

The overall goal of this proposal is to study the mechanisms by which partially reduced oxygen species mediate lung cell injury. Aortic and pulmonary artery endothelial cells and type II aveolar epithelial cells will be used as in vitro models because a data base exists for both the in vitro and in vivo responses of these cell types to oxidant stress. To accomplish this, proposed studies are designed to illuminate biochemical mechanisms of oxidant lung injury. Thus, the following specific aims will be addressed: 1. Establish an endothelial cell and type II aveolar epithelial cell culture models for the study of free radical mediated lung injury. 2. Study cytoplasmically, membrane and extracellularly generated free radicals using EPR techniques. 3. Cellular formation of free radicals will be monitored and modulated using hyperoxia and uncouplers of electron transport. 4. Cellular metabolism of free radicals will be studied using free radical scavengers and by liposome mediated augmentation of intracellular antioxidant defenses. 5. Cellular indices of free radical injury and modulation of injury will be studied using metabolic indicators and EPR measurement of structural changes in membrane microdomains. This research proposal represents a combination of lung cell biology and sophisticated spectroscopic approaches towards the identification of specific free radicals and their affects on membrane structure. Pharmacological manipulation of antioxidant defenses using liposomes containing superoxide dismutase or catalase will be potentially beneficial in many metabolic situations. Finally, completion of the above specific aims will provide insight into the etiology of oxidant lung injury.