The Evaluation of Effective-component Compatibility of Bufei Yishen FormulaⅢ and Components Compatibility in Treating Airway Remodeling of COPD

doi:10.12114/j.issn.1007-9572.2023.0868

Chinese General Practice ›› 2024, Vol. 27 ›› Issue (33): 4196-4203.DOI: 10.12114/j.issn.1007-9572.2023.0868

• Original Research·Combination of Chinese and Western Medicine • Previous Articles Next Articles

The Evaluation of Effective-component Compatibility of Bufei Yishen FormulaⅢ and Components Compatibility in Treating Airway Remodeling of COPD

1. Henan University of Chinese Medicine/Henan Key Laboratory of Chinese Medicine for Respiratory Disease/Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R., Zhengzhou 450046, China
2. Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou 450046, China
3. Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450003, China

Received:2024-01-05 Revised:2024-03-21 Published:2024-11-20 Online:2024-08-08
Contact: LI Jiansheng

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

1．450046　河南省郑州市，河南中医药大学　河南省中医药防治呼吸病重点实验室　呼吸疾病中医药防治省部共建协同创新中心
2．450046　河南省郑州市，河南中医药大学中医药科学院
3．450003　河南省郑州市，河南中医药大学第一附属医院呼吸与危重医学科

通讯作者: 李建生
作者简介:
作者贡献：
李建生提出"组分配伍"的研究思路，设计研究方案；秦燕勤、董浩然进行动物饲养、药物干预、肺功能检测及气道重塑指标测定；杨静帆、李海博负责肺组织病理检测；秦燕勤、杨静帆负责实验数据收集及统计分析；秦燕勤负责论文起草；赵鹏、李建生负责论文修改；秦燕勤、李建生负责最终版本修订，对论文负责。
基金资助:
国家自然科学基金资助项目(82104662，81973822); 河南省科技攻关计划项目(222102310141); 河南省博士后科研项目(202101046)

Abstract

Abstract:

Background

Chronic 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-BYFⅢ and components compatibility in treating airway remodeling of COPD based on the COPD rat model.

Methods

The components of ECC-BYFⅢ 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-BYFⅢ, different components compatibility and aminophylline weakened the thickness of airway wall, when compared to model group. ECC-BYFⅢ, 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-BYFⅢ, Fuzheng groups. The levels of MMP-12, COL-1 in BALF decreased in ECC-BYFⅢ, different components compatibility and aminophylline groups. The level of COL-3 in BALF decreased in ECC-BYFⅢ, 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-BYFⅢ, 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-BYFⅢ 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, Effective-component compatibility of Bufei Yishen formulaⅢ, 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4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。将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。第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）；第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

CLC Number:

R 563.9

QIN Yanqin,DONG Haoran,YANG Jingfan, et al. The Evaluation of Effective-component Compatibility of Bufei Yishen FormulaⅢ and Components Compatibility in Treating Airway Remodeling of COPD[J]. Chinese General Practice, 2024, 27(33): 4196-4203. DOI: 10.12114/j.issn.1007-9572.2023.0868.
秦燕勤,董浩然,杨静帆等. 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[J]. 中国全科医学, 2024, 27(33): 4196-4203. DOI: 10.12114/j.issn.1007-9572.2023.0868.

Figures/Tables 5

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组别	只数	气道壁厚度（μm）	平均气道平滑肌细胞数（个/mm）
正常组	6	24.79±4.70	14.65±4.32
模型组	6	36.27±4.27^a	22.02±3.79^a
ECC-BYF Ⅲ组	6	23.09±5.51^b	15.66±4.85^b
补气组	6	17.79±3.22^b	21.93±2.07
补肾组	6	19.44±5.33^b	21.93±7.50
化痰组	6	19.46±5.74^b	20.96±4.80
活血组	6	15.48±5.37^b	17.60±8.28
扶正组	6	16.10±2.47^b	18.34±7.72
祛邪组	6	17.64±3.31^b	20.21±3.79
补气化痰组	6	15.64±2.95^b	16.38±5.70^b
补气活血组	6	17.60±7.67^b	18.39±3.43
补肾化痰组	6	16.09±4.32^b	17.44±3.44
补肾活血组	6	16.79±3.56^b	17.62±5.89
扶正化痰组	6	14.11±1.27^b	15.02±3.43^b
扶正活血组	6	15.21±1.51^b	14.99±1.87^b
补气祛邪组	6	13.30±1.61^b	14.61±3.22^b
补肾祛邪组	6	15.57±3.61^b	16.88±3.37
氨茶碱组	6	26.41±8.03^b	15.34±2.35^b
F值		8.074	1.797
P值		<0.001	0.040

组别	只数	气道壁厚度（μm）	平均气道平滑肌细胞数（个/mm）
正常组	6	24.79±4.70	14.65±4.32
模型组	6	36.27±4.27^a	22.02±3.79^a
ECC-BYF Ⅲ组	6	23.09±5.51^b	15.66±4.85^b
补气组	6	17.79±3.22^b	21.93±2.07
补肾组	6	19.44±5.33^b	21.93±7.50
化痰组	6	19.46±5.74^b	20.96±4.80
活血组	6	15.48±5.37^b	17.60±8.28
扶正组	6	16.10±2.47^b	18.34±7.72
祛邪组	6	17.64±3.31^b	20.21±3.79
补气化痰组	6	15.64±2.95^b	16.38±5.70^b
补气活血组	6	17.60±7.67^b	18.39±3.43
补肾化痰组	6	16.09±4.32^b	17.44±3.44
补肾活血组	6	16.79±3.56^b	17.62±5.89
扶正化痰组	6	14.11±1.27^b	15.02±3.43^b
扶正活血组	6	15.21±1.51^b	14.99±1.87^b
补气祛邪组	6	13.30±1.61^b	14.61±3.22^b
补肾祛邪组	6	15.57±3.61^b	16.88±3.37
氨茶碱组	6	26.41±8.03^b	15.34±2.35^b
F值		8.074	1.797
P值		<0.001	0.040

组别	只数	血清bFGF	血清MMP-12	BALF MMP-12	BALF COL-1	BALF COL-3
正常组	6	247.27±72.26	1 409.90±469.53	406.70±69.78	10.02±2.05	447.22±75.32
模型组	6	379.87±87.18^a	2 273.86±436.32^a	794.00±57.23^a	15.76±3.15^a	707.03±97.30^a
ECC-BYF Ⅲ组	6	269.15±74.42^b	1 518.10±429.33^b	391.37±70.56^b	10.18±0.94^b	440.50±170.70^b
补气组	6	369.73±96.66	1 951.16±459.87	436.31±58.85^b	7.59±2.78^b	556.28±145.62
补肾组	6	249.76±70.18^b	1 712.37±575.88	478.43±71.13^b	9.57±2.24^b	442.96±28.53^b
化痰组	6	304.80±128.29	2 541.04±1 187.88	402.52±62.93^b	9.24±3.39^b	454.00±80.23^b
活血组	6	382.35±89.36	2 124.54±385.73	443.38±58.35^b	8.09±2.27^b	453.34±136.21^b
扶正组	6	370.1±122.11	1 782.55±665.36^b	483.56±79.98^b	8.15±2.05^b	351.09±174.58^b
祛邪组	6	300.32±83.96	2 135.79±720.76	541.85±68.56^b	9.40±0.68^b	615.85±191.74
补气化痰组	6	260.87±61.84^b	1 910.99±436.63	463.14±97.12^b	8.00±2.28^b	397.88±111.35^b
补气活血组	6	259.49±81.83^b	2 081.8±290.78	457.52±38.90^b	7.69±0.89^b	340.87±48.82^b
补肾化痰组	6	234.26±30.57^b	1 924.36±711.25	561.21±105.46^b	8.43±1.57^b	521.27±74.28
补肾活血组	6	271.68±110.95^b	1 975.62±426.10	474.27±55.06^b	8.90±2.06^b	445.40±109.16^b
扶正化痰组	6	362.08±133.30	1 976.51±402.24	452.36±37.07^b	8.63±1.00^b	388.74±57.57^b
扶正活血组	6	292.46±120.40	2 113.15±624.37	511.87±133.53^b	8.98±2.51^b	499.46±155.20
补气祛邪组	6	298.99±55.01	1 885.92±468.08	272.71±41.95^b	6.06±1.55^b	379.20±160.50^b
补肾祛邪组	6	289.54±64.57	2 085.07±668.93	455.32±64.40^b	7.99±1.95^b	373.59±91.55^b
氨茶碱组	6	285.16±88.38	1 920.86±430.40	358.22±44.99^b	6.79±1.03^b	348.98±82.71^b
F值		1.832	2.031	1.781	2.116	2.734
P值		0.040	0.013	0.035	0.009	0.001

组别	只数	血清bFGF	血清MMP-12	BALF MMP-12	BALF COL-1	BALF COL-3
正常组	6	247.27±72.26	1 409.90±469.53	406.70±69.78	10.02±2.05	447.22±75.32
模型组	6	379.87±87.18^a	2 273.86±436.32^a	794.00±57.23^a	15.76±3.15^a	707.03±97.30^a
ECC-BYF Ⅲ组	6	269.15±74.42^b	1 518.10±429.33^b	391.37±70.56^b	10.18±0.94^b	440.50±170.70^b
补气组	6	369.73±96.66	1 951.16±459.87	436.31±58.85^b	7.59±2.78^b	556.28±145.62
补肾组	6	249.76±70.18^b	1 712.37±575.88	478.43±71.13^b	9.57±2.24^b	442.96±28.53^b
化痰组	6	304.80±128.29	2 541.04±1 187.88	402.52±62.93^b	9.24±3.39^b	454.00±80.23^b
活血组	6	382.35±89.36	2 124.54±385.73	443.38±58.35^b	8.09±2.27^b	453.34±136.21^b
扶正组	6	370.1±122.11	1 782.55±665.36^b	483.56±79.98^b	8.15±2.05^b	351.09±174.58^b
祛邪组	6	300.32±83.96	2 135.79±720.76	541.85±68.56^b	9.40±0.68^b	615.85±191.74
补气化痰组	6	260.87±61.84^b	1 910.99±436.63	463.14±97.12^b	8.00±2.28^b	397.88±111.35^b
补气活血组	6	259.49±81.83^b	2 081.8±290.78	457.52±38.90^b	7.69±0.89^b	340.87±48.82^b
补肾化痰组	6	234.26±30.57^b	1 924.36±711.25	561.21±105.46^b	8.43±1.57^b	521.27±74.28
补肾活血组	6	271.68±110.95^b	1 975.62±426.10	474.27±55.06^b	8.90±2.06^b	445.40±109.16^b
扶正化痰组	6	362.08±133.30	1 976.51±402.24	452.36±37.07^b	8.63±1.00^b	388.74±57.57^b
扶正活血组	6	292.46±120.40	2 113.15±624.37	511.87±133.53^b	8.98±2.51^b	499.46±155.20
补气祛邪组	6	298.99±55.01	1 885.92±468.08	272.71±41.95^b	6.06±1.55^b	379.20±160.50^b
补肾祛邪组	6	289.54±64.57	2 085.07±668.93	455.32±64.40^b	7.99±1.95^b	373.59±91.55^b
氨茶碱组	6	285.16±88.38	1 920.86±430.40	358.22±44.99^b	6.79±1.03^b	348.98±82.71^b
F值		1.832	2.031	1.781	2.116	2.734
P值		0.040	0.013	0.035	0.009	0.001

组别	指标数	R综合（血清及BALF指标）	指标数	R综合（总指标）
模型组	5	4.00±0.00	7	4.00±0.00
ECC-BYF Ⅲ组	5	3.25±0.33^a	7	3.19±0.29^a
补气组	5	3.24±0.43^a	7	3.18±0.66^a
补肾组	5	3.18±0.41^a	7	3.21±0.52^a
化痰组	5	3.47±0.63	7	3.41±0.62
活血组	5	3.30±0.54^a	7	3.20±0.60^a
扶正组	5	3.21±0.40^a	7	3.05±0.71^a
祛邪组	5	3.48±0.60	7	3.32±0.74
补气化痰组	5	3.21±0.42^a	7	3.03±0.65^a
补气活血组	5	2.93±0.79^a	7	2.98±0.68^a
补肾化痰组	5	3.35±0.49	7	3.17±0.60^a
补肾活血组	5	3.26±0.39^a	7	3.12±0.57^a
扶正化痰组	5	3.01±0.60^a	7	2.69±0.94^a
扶正活血组	5	3.51±0.40	7	3.04±0.95^a
补气祛邪组	5	2.90±0.75^a	7	2.61±0.96^a
补肾祛邪组	5	3.21±0.59^a	7	3.03±0.68^a
氨茶碱组	5	2.85±0.74^a	7	2.92±0.63^a
F值		6.133		11.008
P值		0.016		0.001

The Evaluation of Effective-component Compatibility of Bufei Yishen FormulaⅢ and Components Compatibility in Treating Airway Remodeling of COPD

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

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组别	只数	灌胃药物及灌胃量
正常组	12	0.9%氯化钠溶液（雄鼠2.0 mL/次，雌鼠1.5 mL/次）
模型组	12	0.9%氯化钠溶液（雄鼠2.0 mL/次，雌鼠1.5 mL/次）
ECC-BYF Ⅲ组	12	人参皂苷Rh1+黄芪甲苷+淫羊藿苷+川陈皮素+丹皮酚（5.50 mg·kg^-1·d^-1）
补气组	12	人参皂苷Rh1+黄芪甲苷（1.18 mg·kg^-1·d^-1）
补肾组	12	淫羊藿苷（3.92 mg·kg^-1·d^-1）
化痰组	12	川陈皮素（0.16 mg·kg^-1·d^-1）
活血组	12	丹皮酚（0.25 mg·kg^-1·d^-1）
扶正组	12	人参皂苷Rh1+黄芪甲苷+淫羊藿苷（5.10 mg·kg^-1·d^-1）
祛邪组	12	川陈皮素+丹皮酚（0.40 mg·kg^-1·d^-1）
补气化痰组	12	人参皂苷Rh1+黄芪甲苷+川陈皮素（1.34 mg·kg^-1·d^-1）
补气活血组	12	人参皂苷Rh1+黄芪甲苷+丹皮酚（1.43 mg·kg^-1·d^-1）
补肾化痰组	12	淫羊藿苷+川陈皮素（4.08 mg·kg^-1·d^-1）
补肾活血组	12	淫羊藿苷+丹皮酚（4.17 mg·kg^-1·d^-1）
扶正化痰组	12	人参皂苷Rh1+黄芪甲苷+淫羊藿苷+川陈皮素（5.26 mg·kg^-1·d^-1）
扶正活血组	12	人参皂苷Rh1+黄芪甲苷+淫羊藿苷+丹皮酚（5.35 mg·kg^-1·d^-1）
补气祛邪组	12	人参皂苷Rh1+黄芪甲苷+川陈皮素+丹皮酚（1.58 mg·kg^-1·d^-1）
补肾祛邪组	12	淫羊藿苷+川陈皮素+丹皮酚（4.32 mg·kg^-1·d^-1）
氨茶碱组	12	氨茶碱（54.00 mg·kg^-1·d^-1）

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