慢性阻塞性肺疾病的鼠模型与临床研究的关系

Correlation of chronic obstructive pulmonary disease mouse models and clinical study

慢性阻塞性肺疾病（COPD）是临床状况复杂，具有多种特征的疾病，是在“气流受限，不完全可逆”，这一共同病理生理特征下统一起来。与肺部对有害气体或有害颗粒的异常炎症反应有关。鼠是最有代表性的动物种类，与人基因极为相似，是提供于实验操控基因表达的最有利的动物。用不同的实验方法可制备多样的COPD鼠模型：①用气管内滴注组织降解酶导致肺损害发展为肺气肿，进一步证明蛋白酶／抗蛋白酶失衡理论；②鼠吸入烟草烟雾和有毒刺激物导致COPD样损伤，暴露因素与品系基因易感有关；③在没有外界刺激下，一些自然基因突变的品系，可自发成肺气肿。无论是单一因素还是多因素共同干预制备鼠模型，都将为研究COPD的基因一环境交互作用，以及COPD的发病机制提供有价值的实验数据及理论。

Chronic obstructive pulmonary disease （COPD） is a muhicomponent disease state characterized by airflow limitation that is not fully reversible under common pathophysiological mechanisms and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. Mice represent the most favored animal species which provide the opportunity to manipulate gene expression, as mice genomes are smilar to human ones. Different experimental approaches are applied in order to make different murine models of COPD. Firstly, the tracheal instillation of tissue-degrading enzymes induces emphysematous lung lesions, adding further proof to the protease-antiprotease imbalance hypothesis. Secondly,inhalation of tobacco smoke and other noxious stimuli in mice induces emphysema-like lesions which appears to be strain-dependent. Thirdly, several mouse strains with naturally occurring genetic mutations develop emphysema spontaneously without external stimuli. These mouse models of COPD can provide valuable experimental and theoretical information on both studying genetic-environmental interaction as well as the pathophyslological mechanisms of disease with COPD.