LUNG INJURY, PERFLUOROCARBONS, AND HEMORRHAGIC SHOCK

这项研究将确定四种趋化细胞因子的作用 (MIPalpha、MCP-1、MIP-2和CINC)在急性肺损伤发生发展中的作用 (ALI)后失血性休克，并将探讨 全氟碳部分液体通气法对这些细胞表达的影响 炎症介质。急性肺损伤(ALI)是一种并发症 发生在高达40%的创伤性手术中 围产期，以及其他与急性严重失血有关的事件。这个 失血引起肺损伤的机制，特别是 中性粒细胞在肺中的募集，人们对此知之甚少。部分 液体通风(PLV)，部分全氟碳气体通风- 充盈肺)目前用于呼吸衰竭患者 改善气体交换和肺机械性能。我们的实验室有 生成了大量动物数据，将全氟碳PLV与 急性肺损伤时的肺保护作用。在…的模型中 失血性休克，我们已经证明PLV减少了中性粒细胞 肺内积聚和毛细血管渗漏。我们假设 失血性休克时急性肺损伤的发生发展 依赖于趋化因子和部分液体的表达 通风会导致这些多肽的减少。 利用失血性休克所致肺损伤的大鼠模型，我们打算 系统地确定中性粒细胞的存在和相关性- 在急性失血后吸引细胞因子。随着肺损伤的发生 出血可能是循环或局部介质活动的结果，两者都是 分析血清和肺组织趋化因子的表达情况。酶联免疫吸附试验和Northern 印迹分析将被用来定量细胞因子和趋化因子- 监管。静脉和气管内阻断抗体研究将 以评估每种蛋白质对中性粒细胞的贡献 堆积和毛细管渗漏。一旦相关的趋化因子 确定后，我们将检查部分液体通风对 这些蛋白质的表达。预期效果更好 趋化因子在失血性休克急性加重期的作用 肺损伤和对抗炎作用的更深入了解 部分液体通风。对于申请者，该计划将提供 在活跃的学术环境中进行高强度的研究训练 以科学方法和技术技能为重点 急性肺损伤研究的必要性及新药评价 呼吸衰竭的治疗方法。

This study will determine the role of four chemoattractant cytokines (MIPalpha, MCP-1, MIP-2, and CINC) in the development of acute lung injury (ALI) following hemorrhagic shock and will explore the impact of perfluorocarbon partial liquid ventilation on the expression of these inflammatory mediators. Acute lung injury (ALI) is a complication occurring in as many as 40 percent of traumatic, intraoperative peripartum, and other events associated with acute severe blood loss. The mechanism by which hemorrhage induces lung injury, specifically the recruitment of neutrophils into the lung, is poorly understood. Partial liquid ventilation (PLV, gas ventilation of partially perfluorocarbon- filled lungs) is currently used in patients with respiratory failure to improve gas exchanges and pulmonary mechanics. Our laboratory has generated a large body of animal data linking perfluorocarbon PLV with a lung-protective effect in the setting of acute lung injury. In a model of hemorrhagic shock, we have shown that PLV decreases neutrophil accumulation and capillary leak in the lung. We hypothesize that the development of acute lung injury in the setting of hemorrhagic shock is dependent on the expression of chemokines and that partial liquid ventilation will result in a reduction of these peptides. Using a rat model of hemorrhagic shock-induced lung injury, we intend to systematically determine the presence and relevance of neutrophil- attracting cytokines following acute blood loss. As lung injury following hemorrhage may be a result of circulating or local mediator activity, both serum and lung chemokine expression will be analyzed. ELISA and Northern Blot analysis will be used to quantify cytokine and chemokine up- regulation. Intravenous and intratracheal blocking antibody studies will be performed to assess each protein's contribution to neutrophil accumulation and capillary leak. Once the relevant chemokines are identified, we will examine the effect of partial liquid ventilation on the expression of these proteins. The expected results are better understanding of the role of chemokines in hemorrhagic shock-induced acute lung injury and greater insight into the anti-inflammatory effects of partial liquid ventilation. For the applicant, this program will provide a period of intense research training in an active academic environment with a focus on the scientific methodological and technical skills necessary for the study of acute lung injury and evaluation of new therapies for respiratory failure.