香烟烟雾对慢性阻塞性肺疾病大鼠肺功能及血清细胞因子水平影响

Effects of Cigarette Smoke on Lung Function and Serum Cytokine Levels in Chronic Obstructive Pulmonary Disease Rat

目的探讨被动吸烟联合气道内注入脂多糖(LPS)法制备大鼠慢性阻塞性肺疾病(COPD)模型过程中,大鼠肺功能及血清中细胞因子水平的变化。方法 72只雄性SD大鼠随机均分为4周、6周、8周模型组,自然愈合3周、6周组和对照组。采用气管内两次注入LPS联合持续熏烟的方法建立COPD大鼠模型,动态监测被动吸烟过程中及停止熏烟后,动物肺功能指标0.3 s用力呼气容积(FEV_(0.3))及其与用力肺活量(FVC)比值(FEV0.3/FVC)的变化;同时用酶联免疫吸附方法检测血清中白细胞介素8(IL-8)、白细胞介素10(IL-10)、肿瘤坏死因子α(TNF-α)含量,并进行相关分析。结果与对照组比较,各模型组FEV_(0.3)、FEV_(0.3)/FVC、IL-10水平降低,IL-8、TNF-α水平升高(P均<0.05);且随着熏烟时间延长细胞因子及肺功能指标变化更为显著。模型组IL-8、TNF-α水平与FEV0.3/FVC呈负相关(P<0.001,r=0.579;P=0.034,r=-0.354)。与对照组比较,自然愈合6周组IL-8、TNF-α水平下降(P均<0.05),IL-10升高(P<0.05),各自然愈合组FEV_(0.3)、FEV_(0.3)/FVC均低于对照组(P均<0.05)。结论香烟烟雾刺激能显著影响COPD大鼠体内细胞因子水平。

Objective To investigate the influence of cigarette smoke on lung function and serum cytokine levels in chronic obstructive pulmonary disease （COPD） rats which were established by the complex stimulation of lipopolysaccharide （LPS） and smoked cigarettes. Methods Seventy-two male SD rats were randomly divided into six groups, 4 weeks, 6 weeks and 8 weeks model group, 3 weeks and 6 weeks natural healing group, and control group. A COPD rat model was established by the complex stimulation of two times LPS injection and smoked cigarettes. The lung function of the rats was measured during passive smoking and quit smoking. At the same time serum interleukin-80L-8）, IL- 10 and tumour necrosis factor-alpha （TNF-α） levels were monitored by Enzyme-linked immunosorbent assay. Correlation analysis concerning cytokine levels and pulmonary function index were conducted. Results Compared with control group, forced expiratory volume in 0.3 second （FEV0.3）, forced expiratory volume in 0.3 second as a percentage of forced vital capacity （FEV0.jFVC） and IL-10 were decreased （P〈0.05）, IL-8 and TNF-α levels were increased in the model groups （P〈0.05）. And as the building time prolonged, the changes of those cytokines and lung function indexes were more obvious than before. IL-8 and TNF-α levels were inversely associated with FEV0.3/FVC（P〈0.001, r=-0.579; P=0.034, r=-0.354）. Compared with control group, IL-8 and TNF-α levels were decreased in the 6 weeks healing group, at the same time IL-10 levels was increased（P〈0.05）, the FEV0.3 and FEV0.3/FVC were decreased in the healing groups （P〈0.05）. Conclusions Cigarette smoke is the primary cause of changes on cytokine levels in this animal model.