Wang Y X, Ji M L, Jiang C Y, Qian Z B
Department of Pathophysiology, Xinxiang Medical University, Xinxiang, Henan, China.
Department of Physiology, Xinxiang Medical University, Xinxiang, Henan, China.
Genet Mol Res. 2016 Aug 19;15(3):gmr7971. doi: 10.4238/gmr.15037971.
Chronic obstructive pulmonary disease (COPD) is a devastating lung disorder characterized by sustained airway flow restriction that is not fully reversible. The precise pathogenic mechanisms are unknown, but it is clear that cigarette smoking and chronic inflammatory stimulation are the major causes of COPD. Lung inflammation associated with COPD involves multiple cytokines, aggregation, and activation of neutrophils in the airway and lung tissue, and release of proteases and oxygen free radicals. In this study, a rat model of COPD was established by daily cigarette smoke exposure plus endotoxin treatment (the experimental group). Respiratory curves were recorded by the BL-420 biological signal collecting and processing system. Furthermore, the contents of inflammatory mediators, intercellular adhesion molecular (ICAM)-1 and interleukin (IL)-1β, in bronchoalveolar lavage fluid (BALF) were determined by enzyme linked immunosorbent assay for experimental, smoke-exposed only (control), and untreated (blank) rat groups. Protein expression levels of ICAM-1 and IL-1β in the lung tissue were also compared among groups by the immunohistochemical streptavidin-peroxidase method. The COPD model rats exhibited severe dyspnea and lung inflammation as evidenced by significantly prolonged expiratory duration, higher respiratory rate, elevated ICAM-1 and IL-1β in BALF, and higher ICAM-1 and IL-1β protein expression in lung tissue compared to control and blank group rats. Chronic cigarette smoke exposure plus endotoxin is a feasible and reliable model of COPD that recapitulates many clinical signs and pathogenic responses. ICAM-1 and IL-1β upregulation are possible early contributors to COPD-associated inflammatory lung injury.
慢性阻塞性肺疾病（COPD）是一种具有破坏性的肺部疾病，其特征是存在持续的、不完全可逆的气道气流受限。确切的致病机制尚不清楚，但很明显，吸烟和慢性炎症刺激是COPD的主要病因。与COPD相关的肺部炎症涉及多种细胞因子、气道和肺组织中中性粒细胞的聚集和激活，以及蛋白酶和氧自由基的释放。在本研究中，通过每日香烟烟雾暴露加内毒素处理建立了COPD大鼠模型（实验组）。用BL-420生物信号采集与处理系统记录呼吸曲线。此外，通过酶联免疫吸附测定法测定实验、仅烟雾暴露（对照）和未处理（空白）大鼠组支气管肺泡灌洗液（BALF）中炎症介质、细胞间黏附分子（ICAM）-1和白细胞介素（IL）-1β的含量。还通过免疫组织化学链霉亲和素-过氧化物酶法比较了各组肺组织中ICAM-1和IL-1β的蛋白表达水平。与对照组和空白组大鼠相比，COPD模型大鼠表现出严重的呼吸困难和肺部炎症，表现为呼气持续时间显著延长、呼吸频率升高、BALF中ICAM-1和IL-1β升高以及肺组织中ICAM-1和IL-1β蛋白表达升高。长期香烟烟雾暴露加内毒素是一种可行且可靠的COPD模型，可重现许多临床症状和致病反应。ICAM-1和IL-1β上调可能是COPD相关炎症性肺损伤的早期促成因素。
