基于组分配伍探讨补肺益肾方阻抑炎症反应治疗COPD机制

慢性阻塞性肺疾病（COPD）是危害公众健康的重大疑难病。中医药治疗优势显著而疗效基础复杂，作用机制有待阐明。补肺益肾方的临床疗效确证、作用机制初步明确。基于组分配伍研究获得初步等效的补肺益肾组分方，拟开展以下研究：①制备肺泡上皮/巨噬细胞炎症反应模型、大鼠COPD模型，从细胞炎症反应、大鼠肺功能、肺脏病理、炎症反应等优化补肺益肾组分方配伍配比；②制备COPD大鼠模型，从肺功能、病理、炎症反应、氧化应激、蛋白酶失衡、内皮功能、粘液分泌、气道重塑等多种病理生理指标综合考察优化的补肺益肾组分方的各组分及其配伍效应特征；③采用细胞分子生物学技术，以脂多糖和/或香烟烟雾诱导气道上皮、肺泡上皮和巨噬细胞为工具，从NF-κB、p38 MAPK等通路介导的炎症反应探讨补肺益肾组分方配伍机制。从“补肺益肾方→有效组分→组分配伍优化→配伍规律与机制”的新角度，阐释补肺益肾方治疗COPD的物质基础与作用机制。

Chronic obstructive pulmonary disease (COPD) is a serious public health problem. Chinese medicine has exerted significant beneficial effects on COPD. Whereas, Chinese medicinal herbs contain complex active compounds, and its precise therapeutic mechanisms remain to be addressed. Bufei Yishen formula (BYF) has been proven effective in treating COPD patients. And its preliminary therapeutic mechanism has been explored in previous work. Based on the effective-component compatibility approach, we got the effective-component compatibility of BYF, which have the same efficacy with BYF. Here, the alveolar epithelial cells and macrophages models of inflammatory response and a rat model of COPD are used to identify the active components, then optimize the proportion of the components to get the optimized effective-component compatibility of BYF. Then, we evaluate the different effect of each component contained in effective-component compatibility of BYF and their combination effect on the respiratory function, histological changes, inflammatory response, oxidative stress, protease-antiprotease imbalance, endothelial dysfunction, mucus hypersecretion, airway remodeling of COPD rats. Finally, we investigate the effect of each component contained in effective-component compatibility of BYF and their combination effect on the inflammatory response and the activation of NF-κB and p38 MAPK pathway in bronchial epithelial cells, alveolar epithelial cells and macrophages induced by cigarette smoke and/or lipopolysaccharide. These results will illustrate the combination mechanisms of effective-component compatibility of BYF. Taken together, we construct the effective-component compatibility of BYF and uncover their combination mechanisms by identifying active components, optimizing their proportion, evaluating the different effect of each component on COPD rat and cell models of inflammatory response, which toward a more comprehensive understanding of effective components and therapeutic mechanisms of BYF in treating COPD.