THE PATHOGENESIS OF ARDS

虽然ARDS的发病机制已被广泛研究， 细胞和分子事件导致的发展 人类急性肺损伤尚未确定， 建议研究有发展为ARDS风险的患者和患有ARDS的患者 试图更好地确定急性肺损伤的机制。 基于来自ARDS患者的可用数据以及体外和体内研究 从急性肺损伤模型的数据，我们假设， ARDS的发展依赖于中性粒细胞， 白细胞引发剂和白细胞之间的协同作用 刺激剂 我们特别提出内毒素 或肿瘤坏死因子可直接刺激中性粒细胞 隔离并引发中性粒细胞，用于随后的刺激， 补体片段。 刺激中性粒细胞释放02 代谢和蛋白酶，这两者都可以导致细胞损伤 直接. 02代谢物也可以间接地增强损伤， 激活补体，刺激中性粒细胞，局部， 灭活抗蛋白酶。 黄嘌呤氧化酶可能被释放 从刺激或损伤的内皮细胞， 更多的O2代谢物。 这一过程可以通过现有的 和刺激的抗氧化剂清除剂。 细胞的变化 对内毒素的反应性可增强或淬灭该级联反应。 将讨论的具体问题包括： a. 是补体片段、内毒素和肿瘤坏死因子 在ARDS的发展中起重要作用？ B.嗜中性粒细胞对内毒素的反应是否 在ARDS的发展中起重要作用？ C.血液氧化-抗氧化平衡是否发生改变 特别是在ARDS的发展过程中 D.血液蛋白酶和抗蛋白酶活性的改变 在ARDS的发展中起重要作用？ e.对上述因素的分析是否提供了充分的 为深入了解肺损伤的机制提供理论依据 在治疗期间使用特定的干预治疗， 患者有发生ARDS的风险， 预防综合症的发展

Although the pathogenesis for ARDS has been extensively studied, the cellular and molecular events that lead to the development of the acute lung injury in humans have not yet been determine We propose to study patients at risk for developing ARDS and with ARDS to try to define better the mechanism of the acute lung injury. Based on available data from ARDS patients and in vitro and in vivo data from models of acute lung injury, we hypothesize that the development of ARDS is dependent on the neutrophil and results from the synergism between a leukocyte priming agent and a leukocyte stimulating agent. We specifically propose that either endotoxin or tumor necrosis factor may directly stimulate neutrophil sequestration and prime neutrophils for subsequent stimulation by complement fragments. Stimulated neutrophils release 02 metabolities and proteases, both of which can cause cell injury directly. 02 metabolites can also indirectly enhance injury by activating complement, stimulating neutrophils and, locally, inactivating antiproteinases. Xanthine oxidase may be released either from stimulated or injured endothelial cells and generated more 02 metabolites. This process could be modulated by existing and stimulated antioxidant scavengers. Variations in cellular responsiveness to endotoxin could enhance or quench this cascade. The specific questions which will be addressed include: a. Are complement fragments, endotoxin and tumor necrosis factor important in the development of ARDS? b. Are the variations in neutrophil responsibility to endotoxin important in the development of ARDS? c. Do alterations in blood oxidant - anti-oxidant balance occur specifically in the development of ARDS? d. Are alterations in blood protease and antiprotease activity important in the development of ARDS? e. Does the analysis of the above factors provide sufficient insight into the mechanism of lung injury to provide a rationale for the use of a specific intervention therapy during the time a patient is at risk for the development of ARDS in an attempt to prevent the development of the syndrome?