目的 基于表皮生长因子受体/丝裂原活化蛋白激酶/黏蛋白 5AC（EGFR/MAPK/MUC5AC）通路探析益肺 健脾方对慢性阻塞性肺疾病（COPD）大鼠气道黏液高分泌的治疗作用及机制。方法 将 SD 雄性大鼠随机分为 空白组、模型组、氨溴索组及益肺健脾方低、中、高剂量组。烟熏联合脂多糖滴注、番泻叶灌胃泻下的方式复 制肺脾两虚型 COPD 大鼠模型。阿利新蓝-过碘酸-雪夫染色（AB-PAS）观察大鼠支气管黏液分泌及杯状细胞增 生程度；苏木精-伊红染色（HE）观察大鼠肺组织病理形态；蛋白质免疫印迹法（Western Blot）检测大鼠肺组织 MUC5AC、EGFR 蛋白和 c-Jun 氨基末端激酶（JNK）、p38 丝裂活化蛋白激酶（p38 MAPK）、细胞外调节蛋白激 酶（ERK）蛋白及磷酸化蛋白的表达；采用实时荧光定量 PCR 法（RT-qPCR）检测大鼠肺组织 EGFR、JNK、 p38 MAPK、MUC5AC 及 ERK mRNA 的表达。结果 AB-PAS 染色显示氨溴索组及益肺健脾方各剂量组杯状细 胞增生明显改善。HE 染色下见氨溴索组及益肺健脾方高剂量组明显改善肺组织病理损伤。相较于空白组，模 型组肺组织中 ERK、MUC5AC、p38 MAPK、JNK 及 EGFR mRNA 的表达皆明显升高（P＜0.01），MUC5AC、 EGFR 蛋白和 p38 MAPK、JNK、ERK 蛋白及磷酸化蛋白表达量皆明显升高（P＜0.01）。相比于模型组，氨 溴索组及益肺健脾方中、高剂量组各蛋白表达量明显下降（P＜0.01，P＜0.05），低剂量组 EGFR、p38 MAPK、 p-p38 MAPK 蛋白表达量皆降低（P＜0.01，P＜0.05）；高剂量组与氨溴索组 EGFR、ERK、JNK、p38 MAPK 及 MUC5AC mRNA 的表达皆降低（P＜0.01，P＜0.05），中、低剂量组 MUC5AC mRNA 的表达下降（P＜0.05）。结 论 益肺健脾方可减少 MUC5AC 的表达，从而改善气道黏液高分泌，其作用机制与 EGFR/MAPK 信号通路 有关。

Objective To explore the therapeutic effects and mechanism of Yifei Jianpi Prescription on airway mucus hypersecretion in chronic obstructive pulmonary disease （COPD） rats through the epidermal growth factor receptor/ mitogen-activated protein kinase/mucin 5AC （EGFR/MAPK/MUC5AC） pathway. Methods Male SD rats were randomly divided into blank group，model group，ambroxol group and Yifei Jianpi Prescription low-，medium- and high-dose groups. The COPD rat model with lung and spleen deficiency was replicated by smoking combined with lipopolysaccharide instillation and administration of Folium Sennae. Alcian blue-periodic acid-Schiff staining （AB-PAS） was used to observe bronchial mucus secretion and the degree of goblet cell hyperplasia in rats. Hematoxylin-eosin staining （HE） was used to observe the pathological morphology of lung tissue of rats. Western Blot was used to detect the expression of MUC5AC，EGFR protein，c-Jun N-terminal kinase （JNK），p38 MAPK， protein and phosphorylated protein of extracellular regulated protein kinase （ERK） in rat lung tissues. Real-time fluorescence quantitative PCR （RT-qPCR） was used to detect the mRNA expression of EGFR，JNK，p38 MAPK， MUC5AC，and ERK in rat lung tissues. Results AB-PAS staining showed that the number of goblet cells decreased significantly in ambroxol group and all dose groups of Yifei Jianpi Prescription. HE staining showed that ambroxol group and Yifei Jianpi high-dose group significantly improved the pathological injury of lung tissue. Compared with the blank group， the mRNA expressions of ERK， MUC5AC， p38 MAPK， JNK and EGFR were significantly increased in the lung tissues of the model group （P＜0.01），and the expression of MUC5AC and EGFR protein，as well as p38 MAPK，JNK，ERK total and phosphorylated protein were significantly increased （P＜0.01）. Compared with model group，the protein expression levels of ambroxol group and Yifei Jianpi Prescription medium- and highdose groups were significantly decreased （P＜0.01，P＜0.05），while the protein expression levels of EGFR，p38 MAPK and p-p38 MAPK in Yifei Jianpi Prescription low-dose group were decreased （P＜0.01， P＜0.05）. The mRNA expression of EGFR， ERK， JNK， p38 MAPK and MUC5AC in Yifei Jianpi Prescription high-dose and ambroxol groups were decreased （P＜0.01，P＜0.05），and the mRNA expression of MUC5AC in medium- and low-dose groups were decreased （P＜0.05）. Conclusion Yifei Jianpi Prescription can reduce the expression of MUC5AC and improve hypersecretion of airway mucus. Its mechanism is related to the EGFR/MAPK signaling pathway.

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国家自然科学基金项目（82274500）；安徽高校自然科学研究重点项目（KJ2020A0425）；安徽省高等学校自然科学研究重点项目 （2022AH050493）；王胜安徽省名中医工作室项目。