基于miR–146a-5p靶向EGFR/MEK/ERK通路探讨补肺益肾方调控气道黏液稳态治疗COPD机制

慢性阻塞性肺疾病（COPD）是危害公众健康的重大疾病，目前仍缺乏有效疗法。气道黏液高分泌是COPD重要病理基础和重要病理生理机制。前期研究显示补肺益肾方治疗COPD疗效确切，其有效组分可显著改善COPD大鼠黏液高分泌，但该方对气道黏液稳态的作用及机制尚需进一步深入研究。基于前期研究，拟开展：①以COPD模型大鼠为对象，采用免疫荧光、qPCR、WB等技术，测定肺功能，MUC5AC、MUC5B等气道黏液指标及miR-146a-5p、EGFR通路相关指标；②以香烟烟雾诱导的人支气管上皮细胞为对象，采用细胞培养与转染、免疫荧光、qPCR等技术，围绕miR-146a-5p靶向EGFR通路，探讨补肺益肾方对黏液高分泌的作用特点与机制。以揭示补肺益肾方调控miR-146a-5p抑制EGFR/MEK/ERK通路恢复气道黏液稳态治疗COPD的机制，为COPD的补肺益肾方治疗提供新靶点与思路。

Chronic obstructive pulmonary disease (COPD) is a major disease with severe damage to public health, while there is still no effective treatment. Airway mucus hypersecretion is an important pathological basis and an important pathophysiological mechanism of COPD. Previous studies have shown that Bufei Yishen formula had beneficial therapeutic effects on COPD and the effective components of Bufei Yishen formula significantly inhibited the mucus hypersecretion on COPD rats, but the effects and mechanisms of Bufei Yishen formula on airway mucus homeostasis need further study. Based on previous research, the following researches will be carried out: ① Based on a COPD rat model, immunofluorescence, qPCR, WB and other technologies will be used to observe the effects of Bufei Yishen formula in inhibiting airway mucus hypersecretion and explore the mechanisms by measuring the lung function, airway mucus indicators such as MUC5AC, MUC5B, and miR-146a-5p and EGFR pathway related indicators. ② Based on the cigarette smoke-induced bronchial epithelial cells, cell culture and transfection, immunofluorescence, and qPCR techniques will be used to explore the effect and mechanism of Bufei Yishen formula on airway mucus hypersecretion around miR-146a-5p/EGFR/MEK/ERK signaling. This study will reveal the mechanism by which Bufei Yishen formula regulates miR-146a-5p/EGFR/MEK/ERK signaling and restores airway mucus homeostasis to treat COPD. It will provide new targets and ideas for the treatment of Bufei Yishen formula for COPD.