吸烟是COPD的主要危险因素。粘液-纤毛转运系统功能障碍是COPD的重要病理生理改变之一。气道上皮细胞纤毛的长度是维持其正常功能的基础。研究表明健康吸烟者的纤毛长度变短，六个与纤毛形成和结构相关的蛋白质编码基因在健康吸烟人群中基因表达水平有所下调且与纤毛变短存在相关性，但吸烟所致COPD患者的纤毛长度是否发生相同改变及其分子生物学调控机制尚不清楚。该研究拟通过：1.比较健康非吸烟者、健康吸烟者、吸烟COPD患者活检及刷片大气道上皮细胞纤毛长度和6个相关基因表达水平的不同；2.构建吸烟诱导健康上皮细胞纤毛变短的体外培养模型观察其纤毛变短现象以及参与调控基因表达水平的变化；3.构建慢病毒载体感染体外培养的健康吸烟者和吸烟COPD患者气道上皮细胞，外源性地表达前期试验中表达水平下调的纤毛相关基因，观察其纤毛长度变短是否可逆；证实吸烟诱导气道上皮细胞纤毛变短是COPD发病机制的重要环节之一

Cigarette smoking is the major risk factor of COPD. The reduction of mucociliary clearance which is partly maintained by the length of the cilia of the airway epithelial cells is the important pathophysiological change of COPD. Although the previous research has already demonstrated the shorten-length cilia of in vivo large airway epithelial cells which is associated with the down regulation of six cilia related protein coding genes, whether the shorten length cilia as well as the basic molecular regulative mechanism can be founded in smoking COPD patients is still unknown. The present study will try to find the difference of the cilia length and above mentioned six cilia related genes' expression level of the biopsy and brush airway epithelial cells among the groups of health non-smoker, health smoker and smoking COPD patients; to establish the in vitro model of cultured airway epithelial cells with cigarette induced shorten length cilia and observe the pathological characteristics in this progress as well as the involved genetic expression level changes; to express down-regulated cilia related genes ectogenically in cultured airway epithelial cells from health smoker and smoking COPD patients via infected by lentivirus vectors encoding the target genes and then observe whether the shorten of cilia length is reversible. In conclusion, this research is to demonstrate that the cigarette induced shorten length cilia is one of the principal pathogenesis of COPD.