中文摘要：

目的 通过烟草烟雾口鼻暴露联合脂多糖的方法,建立慢性阻塞性肺疾病及相关肺动脉高压（COPD-PH）的小鼠模型.方法 雄性C57B6小鼠24只,按随机数字表法分为对照组和模型组,每组12只,模型组小鼠在第1天和第14天使用细菌脂多糖进行鼻内滴注,置于动物口鼻暴露系统中进行烟草烟雾暴露,对照组小鼠使用生理盐水鼻腔滴注并置于动物口鼻暴露系统中进行正常空气暴露.8周造模结束后,检测肺功能和右心压力,收集小鼠BALF计数炎症细胞总数及细胞类型,观察气道和肺组织病理改变.结果 模型组和对照组小鼠的功能残气量（FRC）分别为（0.402±0.057）和（0.243±0.064） ml （P ＜0.05）,吸气阻力分别为（1.056±0.121）和（0.789 ±0.063）cmH2O·ml-1 ·s-1（1 cmH2O=0.098kPa,P＜0.05）,肺静态顺应性（Cchord）分别为（0.084 ±0.007）和（0.056±0.004） cmH2O/ml（P＜0.05）,右心室平均压（mRVP）分别为（11.3±1.3）和（7.9±1.1）mmHg（1 mmHg =0.133 kPa,P＜ 0.05）,右心室肥厚指数[RV/（LV＋S）]分别为（0.267 ±0.019）和（0.195 ±0.023,P＜0.05）,肺组织切片PAS染色显示模型组杯状细胞增生.模型组小鼠肺组织病理切片可观察到炎症细胞浸润,气管壁和肺细小血管壁平滑肌增厚,提示气管和肺血管重塑的发生.结论 通过应用烟草烟雾口鼻暴露联合脂多糖的方法可以在短时间内建立COPD-PH小鼠模型,并且这种方法更符合于人类的吸烟行为习惯.

英文摘要：

Objective To establish a mouse model of chronic obstructive pulmonary disease （COPD） and associated pulmonary hypertension （COPD-PH） induced by nose-only cigarette smoking exposure plus airway lipopolysaccharide （LPS） inhalation.Methods There were 24 male C57B6 mice divided into a control group and a model group at random.The model group was given LPS by intranasal inhalation on day 1 and day 14 and exposed to the cigarette smoke in a nose-only exposure system, while the control group was given physiological saline and exposed to normal air.The model establishment was evaluated according the following parameters： the lung function and the right heart pressure, the total and differential cell numbers in bronchial alveolar lavage fluid （BALF）, and the pathological changes of lung tissues.Results The functional residual capacity data of the model group and the control group were （0.402 ± 0.057） and （0.243 ± 0.064） ml respectively （P 〈 0.05）.The inspiratory resistance data of the model group and the control group were （1.056 ± 0.121） and （0.789 ± 0.063） cmH2O · ml-1 · s-1 （1 cmH2O =0.098 kPa） respectively（P 〈0.05）.The static lung complimnce data of the model group and the control group were （0.084 ± 0.007）and （0.056 ± 0.004）cmH2 O/ml respectively （P 〈 0.05）.The right ventricular mean pressure of the model group and the control group were（11.3 ± 1.3） and（7.9 ± 1.1） mmHg （1 mmHg =0.133 kPa） respectively（P 〈0.05）, while the right ventricular hypertrophy index of the model group and the control group were（0.267 ± 0.019） and（0.195 ± 0.023） respectively （P 〈 0.05）.Moreover, the histological staining showed that goblet cell hyperplasia, lung inflammation and thickening of smooth muscle layers of bronchial and pulmonary small vessels occurred in the model group, which indicated ongoing airway and blood vessel remodeling.Conclusions A COPD-PH mouse model was established by nose-only cigarette smoking exposure plus airwa