山西医科大学学报2025，Vol.56Issue(2)：134-141,8.DOI:10.13753/j.issn.1007-6611.2025.02.004
过表达IRG1抑制NLRP3炎症小体改善哮喘小鼠气道炎症
Overexpression of IRG1 ameliorates airway inflammation of asthmatic mice by inhibiting NLRP3 inflammasome
摘要
Abstract
Objective To investigate the role and mechanism of immune responsive gene 1(IRG1)in regulating airway inflammation of asthmatic mice.Methods The mice were divided into control group,model group,model+AAV-Ctrl group,and model+AAV-IRG1 group.The recombinant adeno-associated virus(AAV)expressing IRG1 was constructed and injected into the lungs of mice using tra-cheal intubation.The mouse model of asthma was established by ovalbumin(OVA)induction.The expression level of IRG1 protein in lung tissues was measured by Western blot.The content of itaconate in lung tissues was detected by liquid chromatography-mass spec-trometry.The pathological changes in mouse lung tissues were examined by hematoxylin and eosin(HE)staining.The levels of inflam-matory cytokines including interleukin-4(IL-4),IL-5,and IL-13 in the bronchoalveolar lavage fluid(BALF)were detected by enzyme linked immunosorbent assay(ELISA).The number of inflammatory cells in BALF was counted with an automatic cell analyzer.The pro-tein expression levels of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein containing a CARD(ASC),and Caspase-1 in lung tissues were assessed by Western blot.The levels of IL-1β and IL-18 in lung tissues were measured using ELISA.Results Compared with control group,IRG1 expression level and itaconate content were sig-nificantly increased in model group and model+AAV-Ctrl group(P<0.05).Compared with model group and model+AAV-Ctrl group,IRG1 expression level and itaconate content were significantly increased in model+AAV-IRG1 group(P<0.01).Compared with con-trol group,the mice in model group and model+AAV-Ctrl group exhibited thickened tracheal walls,narrowed lumens,and increased infiltration of inflammatory cells around the trachea.Compared with model group and model+AAV-Ctrl group,the tracheal walls of mice were thinned in model+AAV-IRG1 group,lumens were enlarged,and the infiltration of inflammatory cells around the trachea was reduced.Compared with control group,the levels of inflammatory cytokines including IL-4,IL-5,and IL-13 in BALF were signifi-cantly increased(P<0.01),and the numbers of inflammatory cells including eosinophils,neutrophils,and lymphocytes were also sig-nificantly elevated in model group and model+AAV-Ctrl group(P<0.01).Compared with model group and model+AAV-Ctrl group,the levels of inflammatory cytokines and the numbers of inflammatory cells were significantly reduced in model+AAV-IRG1 group(P<0.01).Compared with control group,the expression levels of NLRP3,ASC,Caspase-1,IL-1β,and IL-18 were significantly increased in model group and model+AAV-Ctrl group(P<0.01).Compared with model group and model+AAV-Ctrl group,the expression levels of NLRP3,ASC,Caspase-1,IL-1β,and IL-18 were significantly reduced in model+AAV-IRG1 group(P<0.01).Conclusion IRG1 overexpression can alleviate the airway inflammation in asthmatic mice and improve the pathological damage of lung tissue,which may be related to the inhibition of NLRP3 inflammasome activation.关键词
哮喘/气道炎症/肺组织损伤/IRG1/NLRP3炎症小体/腺相关病毒/衣康酸Key words
asthma/airway inflammation/lung tissue damage/IRG1/NLRP3 inflammasome/adeno-associated virus/itaconate分类
医药卫生引用本文复制引用
陈雪,宁谦..过表达IRG1抑制NLRP3炎症小体改善哮喘小鼠气道炎症[J].山西医科大学学报,2025,56(2):134-141,8.基金项目
陕西省重点研发计划项目(2022SF-141) （2022SF-141）
