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

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.