基于Nrf2/PPARγ信号通路间串话调节巨噬细胞胞葬的补益肺肾方治疗COPD分子机制

巨噬细胞胞葬对结束炎症反应起重要作用，COPD存在巨噬细胞胞葬障碍，PPARγ/Nrf2通路调控巨噬细胞胞葬和炎性反应，参与COPD发生发展，两者相互作用。补肺益肾方可减轻COPD炎症和氧化应激，激活PPARγ通路，抑制巨噬细胞分泌炎症因子。由此，提出假说：PPARγ/Nrf2信号通路失常是COPD巨噬细胞胞葬障碍重要机理，补肺益肾方药可通过调节PPARγ/Nrf2信号通路串话调控巨噬细胞胞葬起到治疗COPD作用。围绕假说，建立大鼠肺巨噬细胞、人THP-1细胞胞葬功能障碍模型，用补肺益肾方，结合通路刺激剂、抑制剂及RNAi、转染和其他细胞分子生物学技术开展体内外研究，比较实验各组炎症反应、氧化应激、巨噬细胞胞葬、胞葬及通路相关分子等变化，阐释Nrf2/PPARγ通路串话对巨噬细胞胞葬调控作用和COPD病理变化的影响，探索补肺益肾方药防治COPD作用分子机制，为治疗COPD提供思路和借鉴

Macrophage efferocytosis plays an important role in resolving inflammatory reaction. COPD has macrophage efferocytosis dysfunction. Crosstalk of PPAR gamma and Nrf2 pathway regulate macrophage efferocytosis and inflammatory response, and participate in COPD development. The prescription of Bufeiyishen can reduce the inflammatory and oxidative stress of COPD, while it can activate the PPAR gamma pathway and inhibit the secretion of inflammatory factors by macrophages. Thus, we hypothesis that PPAR gamma /Nrf2 signal pathway disorder is an important mechanism of COPD macrophage efferocytosis dysfunction, bufeiyishen prescription treat COPD by regulating crosstalk of PPAR gamma /Nrf2 signaling pathway mediated macrophage efferocytosis. On the hypothesis, the rat lung macrophage and THP-1 cell efferocytosis dysfunction model will be established, Bufei Yishen prescription will be applied，combining with the stimulants and inhibitors of pathway and RNAi, transfection and other molecular biology technology to study in vitro and in vivo. The inflammation, oxidative stress, macrophage efferocytosis，efferocytosis and pathway related molecules will be compared in the experimental groups.The research shall be interpretate regulation of macrophage efferocytosis by Nrf2/PPAR gamma pathway crosstalk and the effect on COPD pathology, and explore molecular mechanism of bufeiyishen prescription therapy for COPD ,which provide ideas and reference for the treatment of COPD