Lung Contusion-Mechanisms and Interaction with Aspiration

描述（由申请人提供）： 肺挫伤是胸部钝伤后最常见的损伤，需要住院治疗。肺挫伤的发病机制和细胞机制尚未得到很好的理解，部分原因是缺乏可靠的孤立性肺挫伤的小动物模型。我们最近开发了一种可重复的大鼠模型，用于闭合胸部钝性创伤引起的孤立性双侧肺挫伤，以便于机制研究，该模型用于研究肺挫伤的机制性炎症病理生理学，以及其与胃吸入的相互作用，这在创伤患者中常见。基于我们的初步研究，我们假设孤立性肺挫伤的急性炎症损伤在7天内消退。在存在额外的“二次打击”（如胃吸入）的情况下，这种损伤进展为严重呼吸功能障碍（ALI/ARDS）。具体目标#1详细检查了大鼠模型中的细胞机制（中性粒细胞和肺泡巨噬细胞的作用）和特异性趋化因子（CINC-1、MIP-2和MCP-1）。具体目标#2研究了大鼠肺挫伤与酸和颗粒吸入损伤的相互作用。本研究旨在探讨中性粒细胞、肺泡巨噬细胞和趋化因子（CINC-1、MIP-2和MCP-1）在这两种损伤相互作用中的作用。此外，aim 2使用基因组分析来确定在有/无胃吸入的肺挫伤发病机制中可能重要的其他因素。动物研究在特定目标#3中得到了对钝性创伤伴肺挫伤患者的观察性前瞻性研究的补充。这项流行病学研究还将研究无证胃误吸的危险因素，并检查可能与肺挫伤进展为ALI/ARDS相关的其他危险因素。了解肺挫伤及其与胃误吸的相互作用，创伤患者遭受的两种常见的侮辱，将大大有助于新的诊断和治疗模式的发展。

DESCRIPTION (provided by applicant): Lung contusion is the commonest injury following blunt trauma to the chest that requires admission to the hospital. The pathogenesis and cellular mechansims of lung contusion are not well understood in part due to a lack of a reliable small animal model for isolated lung contusion . We have recently developed a reproducible rat model for isolated bilateral lung contusion from blunt trauma in a closed chest to facilitate mechanistic studies.This model is used here to examine the mechanistic inflammatory pathophysiology of lung contusion, as well as its interaction with gastric aspiration, a frequent occurence in trauma patients. Based on our preliminary studies, we hypothesize that acute inflammatory injury in isolated lung contusion resolves by 7 days. In the presence of an additional "second hit" such as gastric aspiration, this injury progresses to severe respiratory dysfunction (ALI/ARDS). The Specific Aim #1 examines in detail the cellular mechanisms(role of neutrophils and alveolar macrophages) and specific chemokines(CINC-1, MIP-2 and MCP-1) in the rat model. The Specific Aim # 2 studies the interaction of lung contusion with combination of acid and particulate aspiration injury to the lung in rats. This aim examines the role of neutrophils, alveolar macrophages and chemokines (CINC-1, MIP-2 and MCP-1) in the interaction of these two insults. In addition, aim 2 uses genomic profiling to identify other factors that may be important in the pathogenesis of lung contusion with/without gastric aspiration. Animal research is complemented In Specific Aim # 3 by a observational, prospective study in blunt trauma patients with lung contusion . This epidemiological study wil also study the risk factors for unwitnessed gastric aspiration and examine other risk factors that may be associated with the progression of lung contusion to ALI/ARDS. Understanding lung contusion and its interaction with gastric aspiration, two common insults suffered by trauma patients, will greatly aid the development of new diagnostic and therapeutic modalities.