COPD发病率、死亡率高，缺乏有效治愈手段，给社会带来严重经济负担，其原因在于COPD患者肺功能进行性下降。而气道平滑肌细胞过度增殖导致的气道重塑是其重要原因。MK是一种新型肝素结合生长因子，可趋化炎症细胞，参与内炎症反应，与Notch通路相关，而Notch信号能促进肺泡上皮细胞中α平滑肌肌动蛋白及胶原的表达，MK-Notch是否调参与气道平滑肌细胞增殖过程尚不清楚。前期实验中发现COPD大鼠模型气道平滑肌细胞内及其周围MK高表达，MK很可能与Notch通路共同作用，抑制气道平滑肌细胞凋亡及促进增殖加速气道重塑；阻断MK表达或抑制Notch活性，可能阻止气道重塑进程，改善肺功能状态。本课题拟应用COPDSD大鼠、MK反义寡脱氧核苷酸及MK基因敲除小鼠，采用流式、免疫荧光、PCR及WB技术，观察MK-Notch与气道平滑肌细胞增殖的关系，为降低COPD患者气道重塑，改善肺功能提新的治疗方法。

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide with no effective treatment, imposing an enormous economic burden on society. A major reason for lung function decline in COPD is airflow obstruction due to airway remodeling which includes an increased airway smooth muscle (ASM) mass. Midkine(MK) is a heparin-binding growth factor involved in systemic inflammation and can promote the expression of alpha-smooth muscle actin and collagen in alveolar epithelial cells through Notch pathway. However, it is not clear whether the Midkine-Notch pathway could work in airway smooth muscle cells. Previous study on COPD rat model has shown that Midkine highly expressed around airway smooth muscle cells (ASMCs), possibly through the Notch pathway, lead to decrease apposis and over proliferation of the ASMCs and replacement of collagen, increasing the speed of airway remodeling. However, it remains elusive whether block of the expression of midkine would decrease the process of airway remodeling. In this study, we explored the proliferation of ASMCs, expression of alpha-smooth muscle actin and collagen and the relationship with Notch pathway using Flow Cytometry, immunofluorescence,PCR and western blot in mice with knockdown of midkine gene expression by means of antisense oligonucleotide, which implicates new strategies to treat COPD.