Comprehensive analysis of elastase-induced pulmonary emphysema in mice: Effects of ambient existing particulate matters
Comprehensive analysis of elastase-induced pulmonary emphysema in mice: Effects of ambient existing particulate matters
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DOI：
10.1016/j.intimp.2010.07.016
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发表时间：
2010-11-01
影响因子：
5.6
通讯作者：
Takano, Hirohisa
中科院分区：
文献类型：
--
作者：
Inoue, Ken-ichiro;Koike, Eiko;Takano, Hirohisa
啮齿类动物的肺部暴露于猪胰弹性蛋白酶（PPE）会诱发形态上类似于人类全腺泡性肺气肿的病变。然而，对该模型进行综合分析的工作却很少。本研究旨在广泛研究 PPE 对小鼠肺部炎症、细胞损伤、肺气肿变化和胆碱能反应性的生物学影响。此外，我们评估了肺部暴露于柴油机尾气颗粒（DEP）对疾病模型的影响。气管内施用 PPE 诱导 (1) 肺部促炎反应，其特征是白细胞显着浸润，如巨噬细胞、嗜酸性粒细胞和淋巴细胞，以及肺匀浆中白细胞介素 1 β 水平升高；(2) 肺细胞损伤，表现为肺匀浆中总蛋白、乳酸脱氢酶和碱性磷酸酶水平升高；(3) 肺气肿相关的形态学变化，包括气腔扩大和肺气肿相关形态变化。肺泡壁结构的进行性破坏，以及（4）气道对乙酰甲胆碱的反应性在呼吸系统顺应性值的背景下以剂量依赖性方式呈现总体趋势。单次气管内给予 DEP 并没有显着促进该疾病的特征。这是第一项广泛分析 PPE 引起的小鼠肺气肿并评估 DEP 效果的研究。此外，这种生物测定可应用于评估肺气肿新治疗药物或危险因素的未来研究。 (C) 2010 Elsevier B.V. 保留所有权利。
Pulmonary exposure of rodents to porcine pancreatic elastase (PPE) induces lesions that morphologically resemble human panacinar emphysema. However, there has been little work on the comprehensive analysis of this model. The present study was designed to extensively examine the biological effects of PPE on inflammation, cell damage, emphysematous change, and cholinergic reactivity in the lungs of mice. Furthermore, we evaluated the effects of pulmonary exposure to diesel exhaust particles (DEP) on the disease model. Intratracheal administration of PPE induced (1) proinflammatory response in the lungs that was characterized by significant infiltration of leukocytes such as macrophages, eosinophils, and lymphocytes and an increased level of interleukin-1 beta in lung homogenates, (2) lung cell damage, indicated by higher levels of total protein, lactate dehydrogenase, and alkaline phosphatase in lung homogenates, (3) emphysema-related morphological changes including airspace enlargement and progressive destruction of alveolar wall structures, and (4) airway responsiveness to methacholine in the context of the compliance value of the respiratory system in a dose-dependent manner showing an overall trend. A single intratracheal administration of DEP did not significantly facilitate the hallmark of the disease. This is the first study to extensively analyze PPE-induced lung emphysema in mice with evaluation of the effects of DEP. Furthermore, this bioassay may be applied to future investigations that evaluate new therapeutic agents or risk factors for pulmonary emphysema. (C) 2010 Elsevier B.V. All rights reserved.