Abstract: Background Obstructive pulmonary disease（COPD）is a major chronic disease，and airway remodeling is an important pathological mechanism. Bufei Yishen formula and effective-component compatibility of Bufei Yishen formula Ⅲ（ECC-BYF Ⅲ）are effective for COPD treatment. ECC-BYF Ⅲ significantly improves airway remodeling of COPD model rats，however，the components compatibility remains to be revealed. Objective To evaluate the effect of ECC-BYF Ⅲ and components compatibility in treating airway remodeling of COPD based on the COPD rat model. Methods The components of ECC-BYF Ⅲ were divided into four categories：Buqi，Bushen，Huatan，and Huoxue. The four categories were divide into different groups according to the method of mathematical permutation. The animal experiment were performed during May to September in 2018. 216 SD rats were randomly divided into normal，model，ECC-BYF Ⅲ，different components compatibility and aminophylline groups，and 12 rats in each model. From week 1 to week 8，rat model of COPD in stable phase was established by cigarette smoke exposure combined with repeated bacterial infections. The rats were orally gavaged with corresponding drugs from week 9 to week 16. Hematoxylin eosin（HE）staining technique was used to observe the changes of bronchial wall and airway smooth muscle. Enzyme linked immunosorbent assay（ELISA）was used to detect the levels of matrix metalloprotein 12（MMP-12），basic fibroblast growth factor（bFGF）in serum and levels of collagen（COL）-1，COL-3，and MMP-12 in bronchoalveolar lavage fluid（BALF）. Region（R）value comprehensive evaluation method was used to evaluate the effect of different component compatibility on airway remodeling in COPD rats. Results ECC-BYF Ⅲ，different components compatibility and aminophylline weakened the thickness of airway wall，when compared to model group. ECC-BYF Ⅲ，Buqi Huatan，Fuzheng Huatan，Fuzheng Huoxue，Buqi Quxie and aminophylline significantly decreased the number of airway smooth muscle hyperplasia（P<0.05）. When compared to model group，the level of bFGF in serum decreased in ECC-BYF Ⅲ，Bushen，Buqi Huatan，Buqi Huoxue，Bushen Huatan，and Bushen Huoxue groups. The level of MMP-12 in serum decreased ECC-BYF Ⅲ，Fuzheng groups. The levels of MMP-12，COL-1 in BALF decreased in ECC-BYF Ⅲ，different components compatibility and aminophylline groups. The level of COL-3 in BALF decreased in ECC-BYF Ⅲ，Bushen，Huatan，Huoxue，Fuzheng，Buqi Huatan，Buqi Huoxue，Bushen Huoxue，Fuzheng Huatan，Buqi Quxie，Bushen Quxie，and aminophylline groups（P<0.05）. The results of R-value comprehensive evaluation about airway wall thickness，airway smooth muscle hyperplasia，indicators related to airway remodeling in serum and BALF in COPD rats showed that the components compatibility，except for Huatan，Quxie，ECC-BYF Ⅲ，other components compatibility and aminophylline improved the airway remodeling of COPD rats（P<0.05）. Buqi Quxie，Fuzheng Huatan，and Buqi Huoxue showed better effects in improving airway remodeling in COPD rats. Conclusion ECC-BYF Ⅲ and its components compatibility showed different effects on airway remodeling in COPD rats. Buqi Quxie，Fuzheng Huatan，Buqi Huoxie（containing ginsenoside Rh1，astragaloside）showed better effects.

Key words: Pulmonary disease, chronic obstructive；ECC-BYF Ⅲ；Airway remodeling；Components compatibility；Rats

摘要： 背景 慢性阻塞性肺疾病（COPD）是重大慢性疾病，气道重塑是其重要病理机制。补肺益肾方对COPD 疗效较好，其有效成分组成的补肺益肾组分方Ⅲ（ECC-BYF Ⅲ）与之疗效相当，可显著改善 COPD 模型大鼠气道重塑，但其组分配伍规律尚待揭示。目的 基于 COPD 大鼠模型评价 ECC-BYF Ⅲ及其组分配伍对 COPD 气道重塑的干预作用。方法 将 ECC-BYF Ⅲ组分分成补气、补肾、化痰、活血四类，按数学排列组合的方法将其分成不同的组分配伍组。2018 年 5—9 月进行动物实验。216 只 SD 大鼠随机分为正常、模型、ECC-BYF Ⅲ、不同组分配伍及氨茶碱组，共 18 组，每组 12 只。1~8 周，采用香烟烟雾暴露联合反复细菌感染的方法制备 COPD 稳定期大鼠模型（正常组除外）；9~16 周，给予相应的药物干预。苏木素 - 伊红（HE）染色技术观察气道壁及气道平滑肌变化；酶联免疫吸附试验（ELISA）检测血清中基质金属蛋白酶 12（MMP-12）、碱性成纤维细胞生长因子（bFGF）及支气管肺泡灌洗液（BALF）中胶原蛋白（COL）-1、COL-3、MMP-12 等气道重塑相关指标水平。Region（R）值综合评价各组分配伍对 COPD 大鼠气道重塑的干预作用。结果 与模型组比较，ECC-BYF Ⅲ及其组分配伍、氨茶碱组大鼠气道壁厚度均降低，ECC-BYF Ⅲ组、补气化痰组、扶正化痰组、扶正活血组、补气祛邪组、氨茶碱组大鼠平均气道平滑肌细胞数减少（P<0.05）。与模型组比较，ECC-BYF Ⅲ组、补肾组、补气化痰组、补气活血组、补肾化痰组、补肾活血组血清 bFGF 水平降低，ECC-BYF Ⅲ组、扶正组血清 MMP-12 水平降低，ECC-BYF Ⅲ及其组分配伍、氨茶碱组 BALF MMP-12、BALF COL-1 水平均降低，ECC-BYF Ⅲ组、补肾组、化痰组、活血组、扶正组、补气化痰组、补气活血组、补肾活血组、扶正化痰组、补气祛邪组、补肾祛邪组及氨茶碱组 BALF COL-3 水平均降低（P<0.05）。对 COPD 大鼠气道壁厚度、气道平滑肌增生情况、血清及 BALF 中所有气道重塑相关指标进行 R 值综合评价结果显示，除化痰、祛邪组分配伍外，ECC-BYF Ⅲ及其余组分配伍和氨茶碱组均可改善 COPD 大鼠气道重塑（P<0.05），以补气祛邪、扶正化痰、补气活血组分配伍改善 COPD 大鼠气道重塑效果较好。结论 ECC-BYF Ⅲ及其组分配伍可不同程度干预 COPD大鼠气道重塑，其中以补气祛邪、扶正化痰、补气活血（均含补气类组分：人参皂苷 Rh1 和黄芪甲苷）组分配伍效果较为显著。

关键词: 肺疾病, 慢性阻塞性；补肺益肾组分方Ⅲ；气道重塑；组分配伍；大鼠