目的 探讨贝母素甲（PME）对慢性阻塞性肺疾病（COPD）小鼠的作用和相关机制。  方法 将80只小鼠随机分为4组（每组20只）：对照组、PME组、COPD组和治疗组。使用脂多糖联合烟雾诱导小鼠COPD动物模型。通过组织病理学、超微结构、小鼠肺组织湿/干重比值分析 PME 对 COPD 模型鼠结构的影响；ELISA和Western blotting分析PME对肺组织中炎症因子肿瘤坏死因子(TNF)-α、白细胞介素( IL) -6和IL-1β表达的影响；二氢乙锭(DHE)染色和Western blotting分析PME对肺组织中氧化应激反应的影响；Western blotting分析PME对核因子κB(NF-κB)通路以及核因子2相关因子2（Nrf2）通路相关蛋白表达的影响。  结果 与COPD组相比，PME治疗可明显减轻小鼠肺组织的损伤和减少炎症细胞数量，降低肺组织湿/干重比。与对照组相比，COPD组小鼠的肺泡灌洗液中TNF-α、IL-6及IL-1β水平明显增加，经PME治疗后小鼠肺泡灌洗液中TNF-α、IL-6及IL-1β水平明显降低。另外，与对照组相比，COPD组小鼠肺组织中TNF-α和IL-1β水平显著升高，经PME治疗后小鼠肺组织中TNF-α和IL-1β蛋白水平明显下降。免疫组织化学和Western blotting实验显示，与对照组相比，COPD组SOD2水平明显降低，而PME治疗后能够提高超氧化物歧化酶(SOD)蛋白水平。对肺组织丙二醛（MDA）含量分析发现，与COPD组比较，PME治疗后明显抑制COPD小鼠肺组织中MDA的产生。Western blotting结果显示，PME治疗后能够阻止肺组织中的NF-κB抑制蛋白（IκBα）磷酸化以及NF-κB p65向细胞核转移，PME处理后的小鼠肺组织中Nrf2及其主要下游靶点血红素加氧酶1（HO-1）的表达明显升高。  结论 PME能够抑制COPD小鼠体内的炎症和氧化应激反应，改善脂多糖联合烟雾诱导肺组织损伤，其机制可能与激活Nrf2通路和抑制NF-κB通路相关。

Objective To investigate the effects and mechanisms of peimine (PME) on chronic obstructive pulmonary disease (COPD) in mice.   Methods The mice were randomly divided into 4 groups (20 mice in each group), control group, PME group, chronic obstructive pulmonary disease group and treatment group. Animal models of COPD were induced in mice by lipopolysaccharide combined with smoke. The effects of PME on COPD model mice was analyzed by HE staining, transmission electron microscopy and the ratio of wet/dry weight of mouse lung tissue. The effects of PME on COPD model mice were analyzed by HE staining, transmission electron microscopy and the ratio of wet/dry weight of mouse lung tissue. The effects of PME on inflammatory factor tumor necrosis factor (TNF)-α, interleukin(IL)-6 and IL-1β in lung tissue were analyzed by ELISA and Western blotting. The effects of PME on oxidative stress in lung tissue were analyzed by dihydroethidium (DHE) staining and Western blotting. The effects of PME on nuclear factor kappa-B (NF-κB) pathway and nuclear factor erythroid 2-related factor 2(Nrf2) pathway were analyzed by protein immunoblotting.      Results Compared with the COPD group, PME treatment could significantly improve the lung tissue injury and the number of inflammatory cells in mice, and the wet/dry weight ratio of lung tissue was significantly reduced. Compared with the control group, the levels of TNF-α, IL-6 and IL-1β in the alveolar lavage fluid of COPD mice significantly increased, and the level of TNF-α, IL-6 and IL-1β in the alveolar lavage fluid of mice after PME treatment was significantly reduced. In addition, compared with the control group, the protein expression of TNF-α, IL-6 and IL-1β in the lung tissue of COPD mice significantly increased, and the level of TNF-α, IL-6 and IL-1β in the lung tissue of COPD mice after PME treatment were significantly reduced. Immunohistochemistry and Western blotting showed that the level of superoxide dismutase 2(SOD2) protein in COPD group was significantly lower than that in control group, while PME treatment could improve the level of superoxide dismutase protein. The analysis of MDA content in lung tissue showed that compared with the COPD group, the production of MDA in lung tissue of COPD mice was significantly inhibited after PME treatment. Protein Western blotting showed that PME treatment could prevent the phosphorylation of inhibitor of NF-κB(IκBα) and the transfer of NF-κB p65 to the cell nucleus, and the expression of Nrf2 and its main downstream target heme oxygenase-1(HO-1) in the lung tissue of mice treated with PME significantly increased.  Conclusion PME is able to inhibit inflammation and oxidative stress and improve lung tissues damage in the COPD model in vivo and this protection effect might be both the Nrf2 pathway activation and NF-κB pathway inhibition.