中国免疫学杂志2025，Vol.41Issue(4)：854-860,7.DOI:10.3969/j.issn.1000-484X.2025.04.014
DEC2缺失促进感染后咳嗽高发及盐酸麻黄碱的治疗作用机制
DEC2 deficiency promotes high incidence of post infectious cough and the therapeutic mechanism of ephedrine hydrochloride
摘要
Abstract
Objective:To explore the mechanism of DEC2 deficiency promoting high incidence of post infectious cough(PIC)and the therapeutic effects of ephedrine hydrochloride(EH).Methods:C57BL/6 wild-type(WT)mice and DEC2-knockout(DEC2-KO)mice were treated with lipopolysaccharide(LPS)nose drops and smoke stimulation to establish PIC models,and some model mice were treated with EH intervention.Counting capsaicin-induced cough at 12,14,16 and 17 day of modeling;Single-cell sequenc-ing,flow cytometry,RT-qPCR and other techniques were used to detect the expressions of IL-1,IL-6,IFN-γ and other inflammatory factors and receptors in the lungs of mice before and after PIC modeling and EH intervention.The expressions of inflammatory factors and their receptors,as well as NF-κB signaling molecules,were analyzed by RT-qPCR using mouse lung CD45-primary cell culture system under LPS stimulation or EH intervention.Results:The transcription of DEC2 was increased in WT-PIC model mice,and the deficiency of DEC2 in DEC2-KO-PIC mice induced the cough frequency 2-fold higher than that in WT-PIC mice.The absence of DEC2 exacerbated LPS-induced pulmonary inflammatory response,especially increased expressions of IL-1,IL-6,IL-1Ra,IL-6Ra,IFN-γR in lung CD45-cells(P<0.01),and excessive activation of NF-κB signal(P<0.01).After EH treatment,the cough frequency in DEC2-KO-PIC mice was significantly reduced(P<0.001),the expression of IL-1,IL-6,IFN-γ in lung and IL-1Ra,IL-6Ra,IFN-γR in pulmonary CD45-cells were down-regulated(P<0.01).The expression and activation of NF-κB induced by DEC2 deletion were sig-nificantly inhibited(P<0.01).Conclusion:The deficiency of DEC2 can activate NF-κB signal and promote the high expression of in-flammatory cytokine and receptors in pulmonary CD45-cells,which is a risk factor in the high incidence of PIC.EH can inhibit the ex-cessive-activation of NF-κB signal and the inflammatory characteristics of lung local stromal cells caused by DEC2 absence,and that is the main part of pharmacological mechanism for effective treatment of EH targeting PIC.关键词
DEC2/感染后咳嗽/肺脏炎症微环境/盐酸麻黄碱Key words
DEC2/Post infectious cough/Pulmonary inflammation microenvironment/Ephedrine hydrochloride分类
医药卫生引用本文复制引用
张庆国,杨雯越,王悦,张玥,姚成芳..DEC2缺失促进感染后咳嗽高发及盐酸麻黄碱的治疗作用机制[J].中国免疫学杂志,2025,41(4):854-860,7.基金项目
国家自然科学基金面上项目(82074088) （82074088）
山东省重点研发计划重大科技创新工程项目(2022CXGC020514). （2022CXGC020514）
