烟草烟雾暴露（CSE）引发的肺部异常炎症是致慢性阻塞性肺疾病（COPD）的重要发病机制，而体内存在的糖皮质激素抵抗导致糖皮质激素不能充分发挥抗炎作用。氧化应激下P38细胞丝裂原活化蛋白激酶（P38MAPK）/激活蛋白-1（AP-1）路径表达增强引发炎症反应是糖皮质激素抵抗的重要原因。大环内酯类药物对慢性气道炎症性疾病具有抗炎作用，其机制尚不明确。我们前期研究显示红霉素下调氧化应激下转录因子AP-1的活性及减轻炎症细胞糖皮质激素抵抗。据此提出假说：红霉素通过下调P38MAPK/AP-1活性减轻CSE引发的糖皮质激素抵抗。课题以红霉素对P38MAPK/AP-1路径影响为切入点，首先观察红霉素对COPD患者单核细胞P38MAPK/AP-1的影响，继而在机制上探讨红霉素对CSE后的单核细胞P38MAPK /AP-1路径作用，以确定其靶点及对糖皮质激素抵抗的影响，研究将进一步阐明大环内酯类抗炎机制。

Chronic obstructive pulmonary disease (COPD)is characterized by enhanced chronic inflammatory response in the airways and the lung to cigarette smoking exposure(CSE), Corticosteroid insensitivity represents a major barrier to the treatment of COPD. The up-regulation of activity of P38MAPK/AP-1 pathway caused by oxidative stress is an important reason. Macrolides have anti-inflammatory effects on chronic airway inflammatory diseases, but the mechanism remain unknown. We have shown that erythromycin has inhibitory effects on inflammation in COPD, suppress activity of transcription factors AP – 1 and restores corticosteroid insensitivity. Therefore we hypothesized that erythromycin could restores corticosteroid insensitivity induce by cigarette smoke via down-regulation of activity of P38MAPK/AP-1. The key point of this study was to observe the effect of erythromycin on the P38MAPK/AP-1 pathway, the first was to look the influence of erythromycin on P38MAPK/AP-1 pathway of Peripheral blood mononuclear cells from COPD patient, then try to identify the molecular mechanism of erythromycin on P38MAPK/AP-1 pathway and corticosteroid insensitivity in U937 monocytic cells. The research will further explore the mechanism of anti-inflammatory effect of macrolide, which would provide new clues for COPD treatment.