补肺益肾组分方Ⅲ调节慢性阻塞性肺疾病黏液高分泌的配伍特点  

Compatibility characteristics of Bufei Yishen formula Ⅲ in regulating chronic obstructive pulmonary disease mucus hypersecretion

作　　者：秦燕勤 李敏艳 田燕歌[1,2] 赵鹏 李康沉 李聪聪 李建生[1,3] Qin Yanqin;Li Minyan;Tian Yange;Zhao Peng;Li Kangchen;Li Congcong;Li Jiansheng(Henan Key Laboratory of Chinese Medicine for Respiratory Disease,Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases co-constructed by Henan province&Education Ministry of P.R.China,Henan University of Chinese Medicine,Zhengzhou 450046,Henan,China;Academy of Chinese Medical Sciences,Henan University of Chinese Medicine,Zhengzhou 450046,Henan,China;Department of Respiratory Diseases,the First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,Henan,China)

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,郑州450046 [2]河南中医药大学中医药科学院,郑州450046 [3]河南中医药大学第一附属医院呼吸科,郑州450046

出　　处：《中华危重病急救医学》2021年第11期1309-1314,共6页Chinese Critical Care Medicine

基　　金：国家自然科学基金(81973822);国家发明专利(ZL 201711088757.0)。

摘　　要：目的评价补肺益肾组分方Ⅲ(ECC-BYFⅢ)阻抑慢性阻塞性肺疾病(COPD)黏液高分泌的配伍特点。方法将ECC-BYFⅢ组分按原方药物功效分成补气(人参皂苷Rh1+黄芪甲苷)、补肾(淫羊藿苷)、化痰(川陈皮素)、活血(丹皮酚)4组,按数学排列组合的方法将其分为不同组分配伍组(14组)。①按随机数字表法将大鼠分为对照组、模型组、ECC-BYFⅢ及不同组分配伍组,共17组。采用香烟烟雾暴露联合反复细菌感染的方法复制COPD稳定期大鼠模型。于制模第9周开始给予相应的药物灌胃,16周结束后取材。用酶联免疫吸附试验(ELISA)检测血清及支气管肺泡灌洗液(BALF)中基质金属蛋白酶9(MMP-9)、基质金属蛋白酶抑制剂1(TIMP-1)水平,以及肺组织和BALF中黏蛋白(MUC)5AC水平。②将人肺上皮细胞BEAS-2B分为空白组、模型组、ECC-BYFⅢ及不同组分配伍组。于相应药物预处理后4 h建立缺氧诱导的BEAS-2B细胞黏液高分泌模型。采用定量聚合酶链反应(PCR)检测MUC5AC、MUC5B、MUC1的mRNA表达。采用Region(R)值综合评价法评价大鼠及BEAS-2B细胞黏液分泌指标。结果①与对照组比较,模型组大鼠血清及BALF中MMP-9显著升高,TIMP-1水平显著降低;肺组织及BALF中MUC5AC显著升高。R值综合评价结果显示,除补气组和补肾组外,ECC-BYFⅢ及其组分配伍均能显著纠正COPD大鼠黏液高分泌,以ECC-BYFⅢ、补肾祛邪、扶正化痰、祛邪组分配伍效果较优(R值分别为2.15±0.42、2.11±0.23、2.16±0.23、2.16±0.55),与模型组(R值:3.00±0.00)比较差异均有统计学意义(均P<0.05)。②与空白组比较,模型组细胞MUC5AC、MUC5B、MUC1的mRNA表达均升高;但不同组分配伍对BEAS-2B细胞黏液分泌没有明显的作用特点。③综合体内外实验,R值综合评价结果显示,ECC-BYFⅢ及其活血、祛邪、补肾活血、扶正化痰、补气祛邪组分配伍可显著纠正COPD黏液高分泌状态(R值分别为2.30±0.43、2.33±0.44�Objective To evaluate the compatibility laws of effective-component compatibility of Bufei Yishen formulaⅢ(ECC-BYFⅢ)in regulating mucus hypersecretion of chronic obstructive pulmonary disease(COPD).Methods According to the efficacy of the original Chinese medicine,the components of ECC-BYFⅢwere divided into four categories:Buqi(Ginsenoside Rh1+Astragaloside),Bushen(Icariin),Huatan(Nobiletin),and Huoxue(Paeonol).The four categories were divided into 14 groups based on the method of mathematical permutation.①The rats were divided into control group,model group,ECC-BYFⅢ,and different components compatibility groups according to the random number table,totaling 17 groups.COPD rat model in stable phase was established by cigarette smoke exposure combined with repeated bacterial infections.The corresponding drugs were given by gavage at the 9th week of modeling,and the samples were collected at the end of the 16th week.The levels of matrix metalloproteinase-9(MMP-9)and tissue inhibitors of metalloproteinase 1(TIMP-1)in serum and bronchoalveolar lavage fluid(BALF),and the levels of mucin(MUC)5AC in lung tissue and BALF were detected by enzyme linked immunosorbent assay(ELISA).②Human lung epithelial cells BEAS-2B were divided into blank group,model group,and different components compatibility groups.Hypoxia-induced mucus hypersecretion model of human lung epithelial cells BEAS-2B was established 4 hours after corresponding drug pretreatment.The mRNA expressions of MUC5AC,MUC5B,and MUC1 were detected by quantitative polymerase chain reaction(PCR).The mucus secretion indexes of rats and BEAS-2B cells were evaluated by Region(R)value comprehensive evaluation method.Results①Compared with the control group,MMP-9 in serum and BALF from the model group were significantly increased,the level of TIMP-1 was significantly decreased,and MUC5AC in lung tissue and BALF were significantly increased.The results of R value comprehensive evaluation showed that except for the Buqi and Bushen groups,ECC-BYFⅢand other compone

关 键 词：基质金属蛋白酶抑制剂1 黏液高分泌 补肺益肾 MUC5AC 配伍特点 川陈皮素 基质金属蛋白酶9 模型组 

分 类 号：R285.5[医药卫生—中药学]