THE PATHOGENESIS OF ARDS

虽然ARDS的发病机制已经被广泛研究， 导致发展的细胞和分子事件 人类急性肺损伤尚未确定 建议对ARDS和ARDS高危患者进行研究 以期更好地阐明急性肺损伤的发病机制。 基于ARDS患者的可用数据以及体外和体内数据 来自急性肺损伤模型的数据，我们假设 ARDS的发生依赖于中性粒细胞，其结果是 白细胞引发剂与白细胞之间的协同作用 刺激剂。我们特别提出，要么内毒素 或肿瘤坏死因子可直接刺激中性粒细胞 隔离和启动中性粒细胞以用于随后的刺激 补体片段。刺激的中性粒细胞释放02 代谢物和蛋白水解酶，两者都会导致细胞损伤 直接去吧。02代谢物还可通过以下途径间接增强损伤 激活补体，刺激中性粒细胞，在局部， 使抗蛋白酶失活。黄嘌呤氧化酶可能会被释放 从受刺激或损伤的内皮细胞中产生 更多的02代谢物。这一过程可以由现有的 刺激了抗氧化剂清道夫。细胞内的变异 对内毒素的反应可以增强或抑制这种级联反应。 将会解决的具体问题包括： A.补体片段、内毒素和肿瘤坏死因子 对急性呼吸窘迫综合征的发展很重要吗？ 中性粒细胞对内毒素的反应有无变化？ 对急性呼吸窘迫综合征的发展很重要吗？ C.血液氧化剂-抗氧化剂平衡是否发生改变 尤其是在急性呼吸窘迫综合征的发展中？ 血液中的蛋白水解酶和抗蛋白水解酶活性的改变 对急性呼吸窘迫综合征的发展很重要吗？ 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发生机制提供理论依据 在治疗期间使用特定的介入疗法 患者有发展为ARDS的风险，试图 预防该综合征的发展吗？

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?