摘要
目的研究咳喘停袋泡颗粒(Kechuanting,KCT)抑制IL-33/ILC2s和致病性T细胞干预过敏性气道炎症的作用机制。方法网络药理学分析KCT干预哮喘的潜在靶点和机制。以OVA诱导过敏性哮喘模型小鼠。组织病理染色观察肺损伤变化;ELISA和荧光定量PCR分别检测Th2型哮喘中关键炎症因子及其mRNA表达水平;Western blot检测MAPK通路中相关蛋白磷酸化水平;流式细胞术检测ILC2s、Th1、Th17、Th2和Treg细胞的比例。结果网络药理学鉴定出KCT治疗哮喘的227个主要活性成分和143个共同靶点,主要富集到MAPK和IL-17等信号通路。进一步验证实验显示,KCT干预明显减轻了哮喘小鼠肺部炎症损伤程度,减少B细胞数量及IL-4、TNF-α、TGF-β的产生,下调肺组织中JNK磷酸化水平以及Il-33、Bcl11b、Rorα、Tcf-7、Jun、MAPK3、MAPK14 mRNA表达。KCT干预减少了哮喘小鼠肺和脾中ILC2s和Th17数量,抑制肺中Th2细胞浸润。结论KCT对过敏性哮喘气道炎症有较好的治疗作用,其机制与抑制IL-33/ILC2s通路、致病性T细胞亚群和JNK-MAPK信号通路相关。
Aim To investigate the mechanisms of Kechuanting granules(KCT)inhibiting the IL-33/ILC2s pathway and pathogenic T cells to intervene in allergic airway inflammation.Methods Network pharmacology was utilized to analyze the potential targets and mechanisms of KCT-treated asthma.Allergic asthma models were induced in mice using OVA.Lung histopathology was conducted to observe injury changes.ELISA and quantitative PCR were utilized to measure key inflammatory factors and their mRNA expression levels in Th2-type asthma.Western blot was used to detect the phosphorylation levels of relevant proteins in the MAPK pathway.Flow cytometry was performed to evaluate the proportions of ILC2s,Th1,Th17,Th2 and Treg cells.Results Network pharmacology identified 227 main active components and 143 key targets of KCT in treating asthma,primarily enriched in signaling pathways such as MAPK and IL-17.Further validation experiments demonstrated that KCT significantly alleviated lung inflammatory injury in asthmatic mice,reduced the number of B cells,production of IL-4,TNF-αand TGF-β,downregulated JNK phosphorylation levels in lung tissue,as well as mRNA levels of Il-33,Bcl11b,Rorα,Tcf-7,Jun,Mapk3 and Mapk14.KCT intervention reduced the numbers of ILC2s and Th17 cells in lungs and spleens of mice,and inhibited Th2 cell infiltration in lungs.Conclusions KCT exhibits therapeutic effects on allergic airway inflammation in asthma,closely associated with the inhibition of the IL-33/ILC2s pathway,pathogenic T cell subsets,and JNK-MAPK signaling pathway.
作者
邹楠婷
吴招
闫晓东
张春菲
张浩洪
莫庆艳
巨鸣谦
徐金柱
万春平
ZOU Nan-ting;WU Zhao;YAN Xiao-dong;ZHANG Chun-fei;ZHANG Hao-hong;MO Qing-yan;JU Ming-qian;XU Jin-zhu;WAN Chun-ping(The First School of Clinical Medicine and School ofChinese Materia Medica,Yunnan university ofChinese Medicine,Kunming 650500,China;Dept of Respiratory Medicine,Yuxi Unicipal Hospital ofTraditional Chinese Medicine,Yuxi Yunnan 653100,China;Zhenxiong County Hospital of Traditional Medicine,Zhaotong Yunnan 657200,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2024年第7期1350-1357,共8页
Chinese Pharmacological Bulletin
基金
云南省科技厅科技计划项目(No 202101AZ070001-195)
云南省科技人才和平台计划项目(No 202105AG070012)。
