湖南中医药大学学报2026，Vol.46Issue(1)：14-22,9.DOI:10.3969/j.issn.1674-070X.2026.01.003
五虎汤调控miR-182-5p表达靶向NOX4/NLRP3/IL-1β信号通路缓解哮喘小鼠气道炎症的作用机制研究
Mechanism of action of Wuhu Decoction in alleviating airway inflammation in asthmatic mice by regulating miR-182-5p expression to target the NOX4/NLRP3/IL-1β signaling pathway
摘要
Abstract
Objective To investigate the mechanism of action by which Wuhu Decoction alleviates airway inflammation in asthmatic mice by regulating the expression of miR-182-5p to target the nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)/NOD-like receptor thermal protein domain associated protein 3(NLRP3)/interleukin-1β(IL-1β)signaling pathway.Methods A total of 42 Balb/c mice were randomly divided into blank group(Group A,n=6)and modeling group(n=36).The mice were sensitized by intraperitoneal injection of house dust mite,and acute asthma attack was induced by polyinosinic-polycytidylic acid to simulate viral infection.Thirty-six successfully modeled mice were further randomized into six subgroups with six mice each:model group(Group B),miR-182-5p agomir group(Group C),MicroRNA Agomir negative control group(Group D),Wuhu Decoction+miR-182-5p agomir group(Group E),Wuhu Decoction+MicroRNA Agomir negative control group(Group F),and Wuhu Decoction group(Group G).Mice in Groups C and D received pure water by gavage and were treated with miR-182-5p agomir or MicroRNA Agomir negative control via intranasal instillation,respectively.Mice in Groups E,F,and G received Wuhu Decoction by gavage,followed by nasal drip of miR-182-5p agomir,MicroRNA Agomir negative control,or diethylpyrocarbonate(DEPC)-treated water,respectively.Mice in Groups A and B were given pure water by gavage and DEPC-treated water via intranasal instillation.All treatments were performed once daily for seven consecutive days,after which the mice were sacrificed for sample collection.General behavioral performance of the mice were observed.HE and Masson staining were used to evaluate airway inflammatory cell infiltration and collagen fiber deposition in mouse lung tissues.Western blot was employed to examine the protein expression levels of NOX4,NLRP3,and IL-1β in mouse lung tissues,and qPCR was used to measure the expression of miR-182-5p.Results Compared with Group A,mice in Group B exhibited significant behavioral changes,including frequent nose scratching,accelerated respiration,abdominal muscle twitching,and even cyanosis of the lips and mouth to varying degrees.In contrast to Group B,mice in Groups C,F,and G showed improved behavioral performance,with occasional nose scratching,reduced respiratory rate,and no wheezing or hypoxia;mice in Group E presented with a markedly decreased and stable respiratory rate;while mice in Group D showed no significant improvement in behavior and maintained a high respiratory rate.Histopathologically,Group B displayed massive inflammatory cell infiltration,bronchial interstitial edema,and obvious collagen fiber deposition around the airways and blood vessels compared with Group A.Compared with Group B,Groups C,F,and G showed alleviated pathological manifestations,with reduced inflammatory cell infiltration,partial resolution of interstitial edema and decreased collagen fiber deposition;these improvements were more pronounced in Group E,with only a small amount of inflammatory cell infiltration,no obvious interstitial edema,and significantly reduced collagen fiber deposition under the bronchi;Group D still had a large number of inflammatory cells observed by HE staining,and the improvement of collagen fiber deposition was not obvious.At the molecular level,compared with Group A,Group B had a significantly decreased expression of miR-182-5p(P<0.05)and increased protein expression levels of NOX4,NLRP3,and IL-1β(P<0.05).Compared with Group B,Groups C,E,F,and G showed elevated expression of miR-182-5p(P<0.05,P<0.001)and downregulated protein expression of NOX4,NLRP3,and IL-1β(P<0.05,P<0.001).In comparison with Group C,Group D had lower expression of miR-182-5p(P<0.05)and higher protein expression levels of NOX4,NLRP3,and IL-1β(P<0.05).Moreover,compared with Group E,Groups F and G exhibited decreased miR-182-5p expression(P<0.05)and upregulated protein expression of NOX4,NLRP3,and IL-1β(P<0.05).Conclusion Wuhu Decoction can ameliorate asthmatic symptoms and reduce airway inflammation in asthmatic mice,which may be associated with promoting the high expression of miR-182-5p and inhibiting the activation of the NOX4/NLRP3/IL-1β signaling pathway.关键词
支气管哮喘/五虎汤/烟酰胺腺嘌呤二核苷酸磷酸氧化酶4/miR-182-5p/NOD样受体热蛋白结构域相关蛋白3/白细胞介素-1βKey words
bronchial asthma/Wuhu Decoction/nicotinamide adenine dinucleotide phosphate oxidase 4/miR-182-5p/NOD-like receptor thermal protein domain associated protein 3/interleukin-1β分类
医药卫生引用本文复制引用
郭超凡,李娇艳,田娅玲,舒文俊,戴孟庭,周娅微,邓婷,董晓斐..五虎汤调控miR-182-5p表达靶向NOX4/NLRP3/IL-1β信号通路缓解哮喘小鼠气道炎症的作用机制研究[J].湖南中医药大学学报,2026,46(1):14-22,9.基金项目
湖南省自然科学基金项目(2024JJ9434) （2024JJ9434）
湖南省卫生健康委员会科研计划项目(D202306018341) （D202306018341）
湖南中医药大学校级科研联合基金项目(2020XJJJ042). （2020XJJJ042）
