机构地区:[1]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,河南省郑州市450046 [2]河南中医药大学中医药科学院,河南省郑州市450046 [3]河南中医药大学第一附属医院呼吸与危重医学科,河南省郑州市450003
出 处:《中国全科医学》2024年第33期4196-4203,共8页Chinese General Practice
基 金: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)。
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-BYFⅢ)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-BYFⅢ及其组分配伍对COPD气道重塑的干预作用。方法将ECC-BYFⅢ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-BYFⅢ、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(b FGF)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-BYFⅢ及其组分配伍、氨茶碱组大鼠气道壁厚度均降低,ECC-BYFⅢ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-BYFⅢ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b FGF水平降低,ECC-BYFⅢ组、扶正组血清MMP-12水平降低,ECC-BYFⅢ及其组分配伍、氨茶碱组BALF MMP-12、BALF COL-1水平均降低,ECC-BYFⅢ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-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(b FGF)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 b FGF
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