一氧化氮合酶在吸烟导致慢性阻塞性肺疾病中作用机制的初步观察

Preliminary investigation on the role of Nitric Oxide Synthase in smoking-induced chronic obstructive pulmonary disease

目的 建立吸烟引起慢性阻塞性肺疾病 (COPD)的地鼠模型 ,观察一氧化氮合酶 (NOS)在肺内的表达情况 ,以探讨 NOS在吸烟导致COPD中的作用机制。方法 雄性叙利亚金黄地鼠 1 5只 ,每天吸烟 2次 ,每次 1 0支香烟。每周 5 d,连续 3个月。同时设不吸烟正常对照组 1 0只。分别于吸烟 1个月、2个月和 3个月后处死动物 ,行肺组织病理学检查并应用显微 -微机图象处理系统进行形态定量。应用免疫组化方法观察肺内诱生型 NOS(i NOS)和内皮型 NOS(e NOS)的表达情况。结果 吸烟组于 3个月时出现慢性支气管炎和肺气肿的病理改变 ,免疫组化结果表明支气管上皮及肺泡巨噬细胞 i NOS呈强阳性表达 ,e NOS则呈弱阳性表达。结论 吸烟可引起 i NOS的过量表达 ,引起肺部损伤 ,导致 COPD的发生。同时大量吸烟可导致肺内小动脉内皮细胞 e NOS的表达减弱 。

? Objective In order to study the role of Nitric Oxide Synthase(NOS) in the pathogenesis of chronic obstructive pulmonary disease,we developed an animal model of chronic obstructive pulmonary disease(COPD) in hamsters by chronic smoke inhalation and observed the expression of the NOS in pulmonary tissue.Methods 25 male hamsters were studied:normal controls( n =10), hamsters intoxicated for 3 months( n =15).The exposed animals were intoxicated 2 times(10 cigarettes per each time) a day,5 days a week.Pulmonary and bronchial morphological changes were observed by light and electron microscopy after 3 months of smoking.The quantitative pathological examination by image analysis was also performed.The expression of inducible NOS(iNOS)and endothelial NOS(eNOS) in pulmonary tissue was observed by immunohistochemical technique.Results 3 months after smoking the animals presented obvious chronic bronchitis and emphysema.iNOS immunoreactivity in bronchial epithelia and macrophages was stronger than that in normal control.eNOS immunoreactivity in endothelia of pulmonary arteriole was weaker than that in normal control.Conclusions Smoking can induce over expression of iNOS in bronchial epithelia and alveolar macrophages and weak expression of eNOS in endothelia of pulmonary arterioles.The former might result in lung injury and COPD,and the latter might relate to pulmonary hypertension. 〔