Lung Contusion-Mechanisms and Interaction with Aspiration

肺挫伤是胸部钝伤后最常见的损伤，需要入院治疗。 医院肺挫伤的发病机制和细胞机制尚不清楚，部分原因是 缺乏可靠的孤立性肺挫伤小动物模型。我们最近开发了一种 闭合胸腔内钝性创伤致孤立性双侧肺挫伤的大鼠模型， 机制研究。该模型在此用于检查炎症的机制性病理生理学。 肺挫伤，以及它的相互作用，胃误吸，一个常见的发生在创伤病人。 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 7天解决。在存在额外的“第二次打击“，如胃吸入，这种伤害， 严重呼吸功能障碍（ALI/ARDS）。具体目标#1详细检查了细胞 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）在大鼠模型中的作用。具体目标#2研究肺挫伤与以下组合的相互作用： 酸和微粒吸入对大鼠肺的损伤。本研究旨在探讨中性粒细胞、肺泡巨噬细胞、 巨噬细胞和趋化因子（CINC-1、MIP-2和MCP-1）在这两种损伤的相互作用中的作用。在 此外，目标2使用基因组分析（表达微阵列辅以定量RT-PCR）， 全肺匀浆，以确定其他途径，可能是重要的发病机制，肺 挫伤伴/不伴胃误吸认识肺挫伤及其与胃的相互作用 误吸，创伤患者遭受的两种常见的侮辱，将大大有助于新的发展。 诊断和治疗方式。

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 (expression microarray complemented by quantitative RT-PCR) on whole lung homogenates to identify other pathways that may be important in the pathogenesis of lung contusion with/without gastric aspiration. 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.