款冬花散对COPD大鼠巨噬细胞极化的影响及其作用机制研究  

Study on the Effect and Mechanism of Kuandonghua Formula on Macrophage Polarization in Rats for Chronic Obstructive Pulmonary Disease

作　　者：宋光玉 钟云青[2] 吴思沁 宋坤珊 黄沛鑫 滕松杏 Song Guangyu;Zhong Yunqing;Wu Siqin;Song Kunshan;Huang Peixin;Teng Songxing(Guangxi University of Traditional Chinese Medicine,Guangxi,Nanning 530200,China)

机构地区：[1]广西中医药大学,广西南宁530200 [2]广西中医药大学附属国际壮医医院,广西南宁530201

出　　处：《中国中医急症》2023年第10期1718-1722,共5页Journal of Emergency in Traditional Chinese Medicine

基　　金：国家自然科学基金地区科学基金(82260903);广西中医药大学博士科研启动基金(2020BS033);广西中医药适宜技术开发与推广项目(GZSY23-49)。

摘　　要：目的 观察款冬花散对慢性阻塞性肺疾病(COPD)模型大鼠肺巨噬细胞极化的影响及TLR4/NF-κB/NLRP3通路在介导巨噬细胞极化过程中的作用。方法 48只SD大鼠随机分为空白组、模型组、罗红霉素组及款冬花散低、中、高剂量组,每组8只。建立COPD(痰热壅肺证)大鼠模型,采用款冬花散干预,HE染色评估肺组织病理改变,ELISA法对肺泡灌洗液中白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)水平和肺组织iNOS、CD10水平进行定量检测,通过免疫组化和RT-PCR检测肺组织Toll样受体4(TLR4)、核转录因子-κB(NF-κB)、NOD样受体热蛋白结构域相关蛋白3(NLRP3)的蛋白和mRNA表达水平。结果 与空白组相比,模型组大鼠BALF中IL-1β、IL-18含量升高,肺组织中一氧化氮合酶(iNOS)含量升高、CD10含量降低,肺组织中TLR4、NF-κB、NLRP3蛋白表达上调(P <0.01),而款冬花散组对COPD(痰热壅肺证)模型大鼠的生物学特征有一定改善作用,在一定程度上改善肺组织炎性改变,降低大鼠BALF中IL-1β、IL-18含量,降低肺组织iNOS含量,升高肺组织CD10含量,下调肺组织TLR4、NF-κB、NLRP3蛋白表达,且以高剂量组较为明显,呈现出一定的量效关系(P <0.05或P <0.01)。结论 款冬花散能通过TLR4/NF-κB/NLRP3通路抑制COPD(痰热壅肺证)大鼠肺巨噬细胞的M1型极化,靶向干预巨噬细胞极化,从而达到治疗作用。Objective:To observe the effect and mechanism of Kuandonghua Formula on macrophage polariza⁃tion in rats for chronic obstructive pulmonary disease(COPD)with the phlegm-heat stagnation syndrome based on TLR4/NF-κB/NLRP3 signal pathway.Methods:A total of 48 rats were randomly divided into the blank group,the model group,the roxithromycin group,the Kuandonghua Formula group at low,middle and high dosage with 8 rats in each group.The rat model of COPD with the phlegm-heat stagnation syndrome was established.HE stain⁃ing was applied to observe the pathological changes of lung tissues.The levels of IL-1βand IL-18 in bronchoalve⁃olar lavage fluid(BALF)and concentrations of iNOS and CD10 in lung tissue were measured using ELISA.The protein and mRNA expression levels of TLR4,NF-κB and NLRP3 in lung tissue were detected by immunohisto⁃chemistry and RT-PCR methods.Results:Compared with the blank group,the model rats showed an increase in IL-1βand IL-18 content in BALF,an increase in iNOS content and a decrease in CD10 content in lung tissue,and an upregulation of TLR4,NF-κB,and NLRP3 protein expression in lung tissue(P<0.01).The Kuandonghua Formula treatment group had a certain improvement on the biological characteristics of the model rats for COPD with the phlegm-heat stagnation syndrome,improving the inflammatory changes of lung tissue in a way,reducing the content of IL-1β,IL-18 in BALF and iNOS content in lung tissue,increasing the content of CD10 in lung tis⁃sue,and downregulating the expression of TLR4,NF-κB,NLRP3 protein in lung tissue.The high-dose group was more obvious,showing a certain dose-effect relationship(P<0.05 or P<0.01).Conclusion:Kuandonghua Formula inhibits M1 type polarization of pulmonary macrophages in rats for COPD with the phlegm-heat stagnation syn⁃drome through the TLR4/NF-κB/NLRP3 pathway,targeting the intervention of macrophage polarization and ulti⁃mately achieving beneficial therapeutic effects.

关 键 词：慢性阻塞性肺疾病 款冬花散 痰热壅肺证 巨噬细胞极化 大鼠 

分 类 号：R285.5[医药卫生—中药学]