补肺益肾组分方Ⅲ组分配伍对慢性阻塞性肺疾病大鼠气道重塑的干预作用研究
he Evaluation of Effective-component Compatibility of Bufei Yishen Formula Ⅲ and Components Compatibility in Treating Airway Remodeling of COPD
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。
Background??Obstructive pulmonary diseaseCOPDis a major chronic diseaseand airway remodeling is an important pathological mechanism. Bufei Yishen formula and effective-component compatibility of Bufei Yishen formula ECC-BYF are effective for COPD treatment. ECC-BYF significantly improves airway remodeling of COPD model ratshoweverthe components compatibility remains to be revealed. Objective??To evaluate the effect of ECC-BYF and components compatibility in treating airway remodeling of COPD based on the COPD rat model. Methods??The components of ECC-BYF were divided into four categoriesBuqiBushenHuatanand 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 normalmodelECC-BYF different components compatibility and aminophylline groupsand 12 rats in each model. From week 1 to week 8rat 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 eosinHEstaining technique was used to observe the changes of bronchial wall and airway smooth muscle. Enzyme linked immunosorbent assayELISAwas used to detect the levels of matrix metalloprotein 12MMP-12basic fibroblast growth factorbFGFin serum and levels of collagenCOL-1COL-3and MMP-12 in bronchoalveolar lavage fluidBALF. RegionRvalue comprehensive evaluation method was used to evaluate the effect of different component compatibility on airway remodeling in COPD rats. Results??ECC-BYF different components compatibility and aminophylline weakened the thickness of airway wallwhen compared to model group. ECC-BYF Buqi HuatanFuzheng HuatanFuzheng HuoxueBuqi Quxie and aminophylline significantly decreased the number of airway smooth muscle hyperplasiaP<0.05. When compared to model groupthe level of bFGF in serum decreased in ECC-BYF BushenBuqi HuatanBuqi HuoxueBushen Huatanand Bushen Huoxue groups. The level of MMP-12 in serum decreased ECC-BYF Fuzheng groups. The levels of MMP-12COL-1 in BALF decreased in ECC-BYF different components compatibility and aminophylline groups. The level of COL-3 in BALF decreased in ECC-BYF BushenHuatanHuoxueFuzhengBuqi HuatanBuqi HuoxueBushen HuoxueFuzheng HuatanBuqi QuxieBushen Quxieand aminophylline groupsP<0.05. The results of R-value comprehensive evaluation about airway wall thicknessairway smooth muscle hyperplasiaindicators related to airway remodeling in serum and BALF in COPD rats showed that the components compatibilityexcept for HuatanQuxieECC-BYF other components compatibility and aminophylline improved the airway remodeling of COPD ratsP<0.05. Buqi QuxieFuzheng Huatanand Buqi Huoxue showed better effects in improving airway remodeling in COPD rats. Conclusion ?ECC-BYF and its components compatibility showed different effects on airway remodeling in COPD rats. Buqi QuxieFuzheng HuatanBuqi Huoxiecontaining ginsenoside Rh1astragalosideshowed better effects.
董浩然、秦燕勤、杨静帆、李海博、赵鹏、李建生
中医学基础医学内科学
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
董浩然,秦燕勤,杨静帆,李海博,赵鹏,李建生.补肺益肾组分方Ⅲ组分配伍对慢性阻塞性肺疾病大鼠气道重塑的干预作用研究[EB/OL].(2024-03-26)[2025-08-11].https://chinaxiv.org/abs/202403.00318.点此复制
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