中国中药杂志2025，Vol.50Issue(15)：4304-4314,11.DOI:10.19540/j.cnki.cjcmm.20250508.401
天山花楸通过TLR4/PI3K/Akt/MMP9信号通路调控哮喘气道炎症的作用机制研究
Mechanism of Sorbus tianschanica in regulating asthmatic airway inflammation through TLR4/PI3K/Akt/MMP9 signaling pathway
摘要
Abstract
To investigate the effects and mechanisms of the water extract from Sorbus tianschanica(STE)on asthmatic airway inflammation,the mice were randomly divided into six groups,including a control group,a model group,a positive drug dexamethasone group(2 mg·kg-1),a low-dose STE group(1 g·kg-1),a medium-dose STE group(2 g·kg-1),and a high-dose STE group(4 g·kg-1).Except for the control group,all groups were subjected to ovalbumin induction to establish an asthma mouse model.The anti-inflammatory effects of STE were evaluated by examining pathological changes in lung tissue and measuring the levels of interleukin(IL)-4 and IL-5 in bronchoalveolar lavage fluid(BALF).Transcriptomic and proteomic methods were further employed to analyze differentially expressed genes and proteins,as well as their associated signaling pathways in lung tissue.Subsequently,the expression changes of key genes were verified by reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and immunohistochemistry and Western blot methods were used to explore the regulatory mechanisms of STE in the pathogenesis of asthma in mice.Molecular docking was performed by using AutoDock Vina software to evaluate the binding affinity of the main active components in STE with the target proteins,including phosphatidylinositol-3-kinase catalytic subunit α(PIK3CA),Toll-like receptor 4(TLR4),protein kinase B1(Akt1),and matrix metallopeptidase 9(MMP9).The results showed significant inflammatory cell infiltration and fibrous tissue proliferation in the lung tissue of mice in the model group.However,these pathological changes were markedly reduced following STE intervention.Compared with those of the control group,the expression levels of IL-4 and IL-5 in the BALF of the model group were significantly increased but notably decreased following STE intervention.Transcriptomic and proteomic analyses identified key genes and proteins associated with allergic asthma,including tumor necrosis factor(TNF),IL-6,TLR4,PIK3CA,and MMP9.RT-qPCR validation revealed that high-dose STE intervention significantly downregulated the expressions of PIK3CA,IL-6,Akt1,MMP9,IL-13,nuclear factor-kappa B(NF-κB),TNF,CXC motif chemokine ligand 1(CXCL1),and TLR4 mRNAs and significantly upregulated the expression of signal transducer and activator of transcription 1(STAT1)mRNA.Western blot and immunohistochemical analyses confirmed that STE significantly downregulated the expressions of MMP9,TLR4,PIK3CA,and phosphorylated protein kinase B(p-Akt)in lung tissue of asthmatic mice.Moreover,molecular docking demonstrated that kaempferol-3,7-diglucoside,isoquercitrin,quercetin-3-gentiobioside,and hyperoside in STE exhibited stable binding affinities with PIK3CA,TLR4,Akt1,and MMP9,suggesting that the active components may exert anti-inflammatory effects by targeting and modulating asthma-related signaling pathways.In summary,STE exerts anti-asthmatic effects by inhibiting the expressions of PIK3CA,MMP9,p-Akt,and TLR4 and regulating the TLR4/PI3K/Akt/MMP9 signaling pathway.关键词
天山花楸/哮喘/气道炎症/TLR4/PI3K/Akt/MMP9信号通路/分子对接Key words
Sorbus tianschanica/asthma/airway inflammation/TLR4/PI3K/Akt/MMP9 signaling pathway/molecular docking引用本文复制引用
王文凯,常军民,马晓丽,李改茹..天山花楸通过TLR4/PI3K/Akt/MMP9信号通路调控哮喘气道炎症的作用机制研究[J].中国中药杂志,2025,50(15):4304-4314,11.基金项目
新疆维吾尔自治区重大科技专项(2022A03007-3) （2022A03007-3）
