芪黄益肺合剂调控气道炎症治疗慢性阻塞性肺疾病的作用机制  

Mechanism of Qihuang Yifei Mixture in Treatment of Chronic Obstructive Pulmonary Disease by Regulating Airway Inflammation

作　　者：陈斌 杨春艳 铁明慧 秦冬冬 景海卿 邢立威 李邵菲 CHEN Bin;YANG Chunyan;TIE Minghui;QIN Dongdong;JING Haiqing;XING Liwei;LI Shaofei(Kunming Municipal Hospital of Traditional Chinese Medicine/Third Affiliated Hospital of Yunnan University of Chinese Medicine,Kunming 650500,China;Yunnan University of Chinese Medicine,Kunming 650500,China)

机构地区：[1]昆明市中医医院/云南中医药大学第三附属医院,昆明650500 [2]云南中医药大学,昆明650500

出　　处：《世界中医药》2025年第2期239-245,251,共8页World Chinese Medicine

基　　金：国家自然科学基金青年科学基金项目(82274374);云南省科技厅-云南中医药大学应用基础研究联合专项资金项目(202101AZ070001-094);云南省科技厅-云南中医药大学应用基础研究联合专项资金青年项目(202101AZ070001-153)。

摘　　要：目的:观察芪黄益肺合剂对慢性阻塞性肺疾病(COPD)小鼠气道炎症及核因子κB(NF-κB)信号通路的影响,探讨其作用机制。方法:C57BL/6小鼠按照随机数字表法分为6组,每组10只。以烟熏联合气管滴注脂多糖的方法制备COPD模型,药物干预28 d后,采用动物肺功能仪测定小鼠肺功能;苏木精-伊红(HE)染色观察肺组织形态变化及气道炎症评分;酶联免疫吸附试验(ELISA)检测肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)和CXC趋化因子配体1(CXCL1)、CXC趋化因子配体2(CXCL2)的含量;实时荧光定量聚PCR(RT-qPCR)检测TNF-α、IL-1β和CXCL1、CXCL2 mRNA表达;蛋白质印迹法检测磷酸化NF-κB p65(p-NF-κB p65)和磷酸化核因子κB抑制蛋白α(p-IκBα)蛋白表达。结果:与正常组比较,模型组0.1秒用力呼气容积(FEV_(0.1))、呼气峰值流速(PEF)及最大呼气中段流量(MMEF)降低(P<0.05);TNF-α、IL-1β、CXCL1和CXCL2的含量升高(P<0.05);TNF-α、IL-1β、CXCL1和CXCL2 mRNA表达增加(P<0.05);p-NF-κB p65和p-IκBα蛋白表达增强(P<0.05)。与模型组比较,芪黄益肺合剂中、高剂量组FEV_(0.1)、PEF和MMEF提高(P<0.05);TNF-α、IL-1β、CXCL1和CXCL2的含量降低(P<0.05);TNF-α、IL-1β、CXCL1和CXCL2 mRNA表达减少(P<0.05);p-κB p65和p-IκBα蛋白表达减弱(P<0.05)。结论:芪黄益肺合剂能减轻COPD气道炎症,其作用机制可能与抑制NF-κB信号通路活化,下调TNF-α、IL-1β、CXCL1和CXCL2 mRNA表达,减少下游炎症细胞趋化和聚集有关。Objective:To observe the effect of Qihuang Yifei Mixture on airway inflammation and the NF-κB signaling pathway in mice with chronic obstructive pulmonary disease(COPD),and to explore its mechanism of action.Methods:C57BL/6 mice were randomly divided into six groups according to a random number table,with 10 mice per group.The COPD model was induced using a smoke inhalation combined with intratracheal instillation of lipopolysaccharide(LPS).After 28 days of drug intervention,lung function was measured using an animal lung function meter.Hematoxylin-eosin(HE)staining was used to observe lung tissue morphology and airway inflammation score.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),CXC chemokine ligand 1(CXCL1),and CXC chemokine ligand 2(CXCL2).Real-time quantitative PCR(RT-qPCR)was used to assess the mRNA expression levels of TNF-α,IL-1β,CXCL1,and CXCL2.Western blot was used to measure the protein expression of phosphorylated NF-κB p65(p-NF-κB p65)and phosphorylated inhibitor of NF-κBα(p-IκBα).Results:Compared with the normal group,the model group showed a decrease in forced expiratory volume in 0.1 second(FEV_(0.1)),peak expiratory flow(PEF),and maximal mid-expiratory flow(MMEF)(P<0.05),an increase in TNF-α,IL-1β,CXCL1,and CXCL2 levels(P<0.05),an increase in TNF-α,IL-1β,CXCL1,and CXCL2 mRNA expression(P<0.05),and an increase in p-NF-κB p65 and p-IκBαprotein expression(P<0.05).Compared with the model group,the high-and medium-dose Qihuang Yifei Mixture groups showed an increase in FEV_(0.1),PEF,and MMEF(P<0.05),a decrease in TNF-α,IL-1β,CXCL1,and CXCL2 levels(P<0.05),a reduction in TNF-α,IL-1β,CXCL1,and CXCL2 mRNA expression(P<0.05),and a reduction in p-NF-κB p65 and p-IκBαprotein expression(P<0.05).Conclusion:Qihuang Yifei Mixture can reduce airway inflammation in COPD,and its mechanism may involve inhibiting the activation of the NF-κB signaling pathway,downregulating the mRNA expression of TNF-α,IL-1�

关 键 词：慢性阻塞性肺疾病 芪黄益肺合剂 气道炎症 核因子ΚB 炎症介质 趋化因子 肺功能 作用机制 

分 类 号：R285.5[医药卫生—中药学] R563[医药卫生—中医学]