目的 探讨细胞外信号调节蛋白激酶 1/2（ERK1/2）抑制药对慢性阻塞性肺病（COPD）小鼠气道高分泌黏蛋白 5ac（muc5ac）的作用机制。方法 检测不同药物干预 7 d 后各组小鼠肺功能指标，白细胞介素 4（IL⁃4）、干扰素γ（IFN⁃γ）水平，HE 染色观察肺组织病理学变化，RT⁃qPCR 检测肺组织 muc5ac、ERK1/2 mRNA 表达水平，Western blot 检测肺组织 muc5ac、ERK1/2、p⁃ERK1/2 蛋白表达水平。结果 与模型组比较，抑制药组和西药组的低 0.3 s 用力呼气量（FEV0.3）、用力肺活量（FVC）、FEV0.3/ FVC、IL⁃4水平升高，IFN⁃γ水平、muc5ac mRNA表达量、muc5ac、p⁃ERK1/2蛋白表达量降低（P < 0.05），且肺组 织病理学变化改善。结论 ERK1/2抑制药通过抑制ERK1/2信号通路，下调muc5ac表达改善COPD症状。

Objective To explore the mechanism of extracellular signal ⁃ regulated protein kinase 1/2 （ERK1/2）inhibitor U0126 on airway hypersecretion of mucin 5ac（muc5ac）protein in chronic obstructive pulmo⁃ nary disease（COPD）mice. Methods The pulmonary function indexes，interleukin 4（IL ⁃4）and interferon γ （IFN⁃γ）levels of each group of mice after 7 days of intervention with different drugs were detected.HE staining to observe the pathological changes of lung tissue. RT⁃qPCR was used to detect the expression levels of muc5ac and ERK1/2 mRNA in lung tissues. Western blotting was used to detect the expression levels of muc5ac，ERK1/2，and p⁃ERK1/2 proteins in lung tissue. Results Compared with the model group，the levels of FEV0.3，FVC，FEV0.3/ FVC and IL⁃4 in the inhibitory drug group and the western drug group were increased，whereas the levelsof IFN⁃γ， muc5acmRNA，and the protein expression levels of muc5ac and p⁃ERK1/2 were decreased（P < 0.05）. The patho⁃ logical changes of lung tissue improved. Conclusion ERK1/2 inhibitors can reduce the expression of muc5ac by inhibiting the ERK1/2 signaling pathway and improve the symptoms of COPD.