气道黏液高分泌是许多呼吸道疾病如哮喘?慢性阻塞性肺疾病等的重要病理学特征，而这类疾病往往伴有支气管收缩产生的气道狭窄，由此引发气道内压力增高，气道壁上皮细胞受压增加?本项目以气液相界面培养的NHBE细胞为研究对象，采用特定压力实验装置间断性作用于NHBE细胞，模拟气道收缩时气道上皮细胞受到的跨细胞压力，通过ELISA、RT-PCR、real-time PCR检测慢性机械压力对以黏蛋白5AC为代表的气道粘液分泌和合成的影响，并以能抑制黏着斑激酶（FAK）表达的siRNA、EGFR特异性抑制剂AG1478，ERK激酶抑制剂PD98059做干预因素，采用siRNA技术、Western blot在分子水平上进一步研究其具体作用机制，项目预期将揭示机械压力在气道黏液高分泌调控机制中作用，为临床应用中尽快、尽早纠正疾病状态下气道收缩狭窄状态的重要性提供有利的理论依据，并为其靶向性治疗提供新的研究方向。

Mucus hypersecretion is an important pathological feature of many respiratory diseases, such as asthma and chronic obstructive pulmonary diseases.Usually airway narrowing exists in these diseases due to bronchoconstriction, which leads to increases in airway pressure and compression on airway epithelial cells.In this study, we applied chronic compressive mechanical stresses in different degrees on normal human bronchial epithelial (NHBE) cells cultured at an air-liquid interface and explore the effect of chronic mechanic stress on the secretion and synthesis of mucin5AC which is one of the most reprentative airway mucin through ELISA,RT-PCR,real-time PCR methods.At the same time, an EGFR kinase inhibitor (AG1478), an ERK kinase inhibitor (PD98059) and short interfering RNA (siRNA) targeted to FAK were given as intervention factors. Then we try to explore the molecular mechanisms through siRNA and Western blot methods.This project is expected to reveal the regulation mechanism of mechanical stress in airway hypersecretion,provide benefit theoretical foundations for correcting airway contracion state as early as possible in diseased conditions, and provide new strategies for the clinical treatment of bronchoconstriction diseases.