基于Nrf2调节巨噬细胞功能探讨补肾防喘片预防AECOPD的“扶正”机制

慢性阻塞性肺疾病急性加重（AECOPD）是COPD死亡和医疗费用增加的主要原因。我们多中心研究证实，补肾防喘片可显著减少AECOPD次数，但机理不明。已知，肺泡巨噬细胞细菌吞噬能力下降和糖皮质激素（GC）敏感性降低是AECOPD发生的重要内因，Nrf2是调控巨噬细胞功能的关键分子。我们前期从淫羊藿（补肾防喘片君药）中发现了一种新的Nrf2激动剂。根据“巨噬细胞与卫气相关”和“卫出下焦”等理论，结合前期工作，我们推测补肾防喘片可补肾气以助卫气，上调Nrf2，调节巨噬细胞功能，进而预防AECOPD。本研究拟评价补肾防喘片对巨噬细胞GC增敏和细菌吞噬的疗效，并分析其与主要疗效指标的相关性；采用免疫印迹、RNA干扰和基因敲除动物等手段，基于Nrf2/HDAC2和Nrf2/MARCO通路，揭示其调节巨噬细胞功能的机理。该研究有助于明确补肾法预防AECOPD的优势环节，丰富 “卫出下焦”的理论内涵。

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the main cause of COPD mortality and medical costs. Our multicenter study confirmed that BSFC tablets can reduce the frenquency of AECOPD, but the mechanism is unknown. Alveolar macrophage phagocytosis of bacteria and decreased Glucocorticoid (GC) sensitivity is an important internal cause of the occurrence of AECOPD, Nrf2 participate in the process of the above. We found a novel Nrf2 agonist from BSFC tablets. According to the theory of "Weiqi derived from of Xajiao", combined with the previous basis, we speculated that BSFC tablets may increase the bacterial phagocytosis of macrophages and GC sensitivity via regulating Nrf2. This study intends to evaluate the effects of BSFcC tablets on COPD macrophage GC sensitivity and bacterial phagocytosis, and analyze the and main clinical efficacy indexes correlation. the Western blot, RNA interference, flow cytometry and Nrf2 gene knockout mice were used to reveal the mechanism via Nrf2/HDAC2 Nrf2/MARCO pathway. This study will prove the advantages of treating AECOPD with Bushen herbs.