基于Jagged/Notch信号通路调控小气道与肺泡上皮异常分化的补肺益肾方治疗COPD的作用机制研究

慢性阻塞性肺疾病(COPD)是严重危害人类健康的疾病，补肺益肾方对其有较好疗效，涉及复杂的作用机制。前期研究发现其抗炎等作用可能与JAK/STAT、NF-κB信号转导路径有关，但不能解释补肺益肾方改善通气、调节T淋巴细胞亚群数量等作用，说明尚存在其他的作用机制。肺小气道上皮的异常分化以及气道重构是COPD关键的病理环节，Jagged/Notch信号通路参与黏液分泌、气道重塑、肺泡上皮间质化等多个病理环节的调控，由此我们推测补肺益肾方可能通过干预Jagged/Notch信号通路对COPD产生治疗作用。因此，我们应用COPD大鼠模型和香烟烟雾提取物与脂多糖联合攻击的细胞模型，采用分子生物学以及免疫学等技术，研究Jagged/Notch信号转导通路相关因子对COPD小气道上皮和肺泡上皮异常分化的调控，从整体-细胞-分子层面，阐释补肺益肾方基于Jagged/Notch信号通路的作用机制和疗效。

Chronic obstructive pulmonary disease(COPD) is a kind of serious diseases. BuFeiYiShen prescription has good effect on COPD, involving in complex mechanisms. Anti-inflammatory effects of BuFeiYiShen prescription might be related to JAK / STAT or NF-κB signaling pathways in previous study. However, these mechanisms can not explain some effects such as improving pulmonary ventilation, regulating distribution or amounts of T lymphocyte subsets in blood and bronchoalveolar lavage fluid. The results show that there are probably other mechanisms underlying these effects. Key pathology of COPD includes of abnormal differentiation of small airway epithelium and airway remodeling, composing of mucus secretion, airway remodeling and alveolar epithelial- mesenchymal transition, et al, which are related to Jagged/Notch signaling pathway. Thus, we speculate that therapeutic effect on COPD of BuFeiYiShen prescription may be interfering with Jagged/Notch signaling pathway. To confirm the hypothesis, a new study program is given to explore whether regulation of Jagged/Notch signaling pathway is one of mechanisms on abnormal differentiation of small airway epithelium and alveolar epithelialium for BuFeiYiShen prescription by in vivo and in vitro methods, such as COPD rat model made by cigarette smoke extract, cell model attacked with cigarette smoke and LPS, indexes assays of molecular biology and immunology, and so on. In a word, based on reseach of overall level, cell level and molecular level, the purpose of the study is to explore the relationship between Jagged/Notch signaling pathway and some efficacy for BuFeiYiShen prescription against COPD.