[A comparative study of two chronic obstructive pulmonary disease mouse models established by different methods].

Objective: To compare chronic obstructive pulmonary disease (COPD) mouse models established by two different methods-cigarette smoke (CS) exposure alone and CS exposure combined with airway instillation of bacterial LPS. Methods: Male C57 mice were randomly divided into control group(CTL group), CS exposure group (CS group) and intra-tracheal LPS instillation combined with CS exposure group (LPS+CS group) according to the random number table, with 8 rats in each group. After the models were established, we measured the lung function and collected the bronchoalveolar lavage fluid (BALF) to detect the number of inflammatory cells and the expression of mucin and inflammatory mediators. HE and PAS staining were performed to observe the pathological changes in airway and lung tissue and to detect the goblet cells in airway, respectively. Results: Total lung capacity (TLC), functional residual capacity (FRC) and airway resistance (RI) of the CS and LPS+CS groups were higher than those of the CTL group, while the FEV(50)/FVC of these 2 groups was lower (P<0.05). Moreover, both RI and FEV(50)/FVC in the LPS+CS group were higher compared with the CS group (P<0.05). HE staining of lung tissue showed that the average alveolar intercept and thickness of small airway wall in the CS and LPS+CS groups were higher compared to the CTL group. In addition, the average alveolar intercept in the LPS+CS group was lower than that in the CS group [(47.86±2.82) μm and (61.94±7.68) μm respectively, P<0.05], but the area of bronchial inflammation of LPS+CS group was higher. The number of total white blood cells, neutrophils, lymphocytes, macrophages and the level of interleukin-6 (IL-6) in BALF of CS and LPS+CS groups were higher than those of CTL group (all P<0.05). Furthermore, the number of neutrophils and IL-6 level in BALF of LPS+CS group were higher in comparison with CS group, while the number of macrophages in BALF of LPS+CS group was lower (P<0.05). PAS staining of lung tissue indicated that the number of goblet cells in large airways of CS and LPS+CS groups increased more significantly compared to the CTL group, and the number of goblet cells in the LPS+CS group was higher than that in the CS group [(0.16±0.02) and (0.09±0.02) respectively, P<0.05]. The expression levels of Muc5ac and Muc5b in BALF of LPS+CS and CS groups were also higher than those of CTL group (P<0.05), and the level of Muc5ac in BALF of LPS+CS group was higher compared with CS group[(2.69±0.72) and (2.19±0.29) respectively, P<0.05]. Conclusions: Combined exposure of LPS and CS for establishing a COPD mouse model could better simulate the pathological characteristics of human COPD during the acute exacerbation period. The COPD mouse model established by CS exposure alone was able to better imitate the basic features of human COPD in the stable period. Researchers could choose a more appropriate modeling method according to different purposes.目的： 对比分析单纯烟草烟雾（CS）暴露和烟草烟雾暴露联合细菌脂多糖（LPS）气道内滴注两种方法建立的小鼠慢性阻塞性肺疾病（慢阻肺）模型的模拟程度。 方法： 将雄性C57小鼠按随机数字表分为对照组、烟草烟雾暴露组（CS组）和脂多糖气管内滴注联合烟草烟雾暴露组（LPS+CS组），每组8只。造模结束后，检测各组小鼠肺功能；收集小鼠BALF，检测其中炎症细胞数以及黏蛋白和炎性因子表达水平；HE染色观察气道和肺组织病理变化；PAS染色检测气道杯状细胞增生情况。 结果： CS和LPS+CS组小鼠肺功能参数肺总量（TLC）、功能残气量（FRC）、气道阻力（RI）均高于对照组，而肺功能参数FEV(50)/FVC均低于对照组（P<0.05），LPS+CS组RⅠ、FEV(50)/FVC高于CS组（均P<0.05）；肺组织HE染色显示CS和LPS+CS组平均肺泡截距增大及小气道周围炎症均高于对照组，LPS+CS组平均肺泡截距[（47.86±2.82）μm]低于CS组[（61.94±7.68）μm]，差异有统计学意义（P<0.05），而LPS+CS组气道周围炎症高于CS组（P<0.05）；CS和LPS+CS组BALF中白细胞总数、中性粒细胞数、淋巴细胞数、巨噬细胞数以及IL-6水平均高于对照组（均P<0.05）；LPS+CS组中性粒细胞数、IL-6水平高于CS组，而LPS+CS组巨噬细胞数低于CS组（均P<0.05）；肺组织PAS染色显示CS和LPS+CS组大气道杯状细胞均明显增加，且LPS+CS组杯状细胞数目（0.16±0.02）高于CS组（0.09±0.02），差异有统计学意义（P<0.05）；LPS+CS组和CS组BALF中Muc5ac、Muc5b表达水平高于对照组（均P<0.05），且LPS+CS组小鼠BALF中的Muc5ac水平（2.69±0.72）高于CS组（2.19±0.29），差异有统计学意义（P<0.05）。 结论： 应用LPS+CS建立小鼠慢阻肺模型的方法更能模拟人类慢阻肺急性加重期的病理特点，而单纯CS暴露建立慢阻肺模型的方法则更能模拟人类慢阻肺稳定期的基本特点，研究者可根据不同的研究目的选择更合适的建模方法。.