摘要
目的:本研究旨在通过网络药理学结合动物实验探讨止嗽散治疗慢性支气管炎的作用机制。方法:利用网络药理学工具,获得止嗽散治疗慢性支气管炎的有效成分、核心靶点和信号通路。建立慢性支气管炎大鼠模型,进行病理染色、ELISA、免疫组织化学、免疫荧光及Western blot试验验证网络药理学预测的主要靶点和信号通路。结果:网络药理学筛选出止嗽散关键有效成分包括槲皮素、山柰酚、木犀草素、β-谷甾醇、7-甲氧基-2-甲基异黄酮、川陈皮素、芒柄花素;核心靶点涉及TP53、TNF、IL-6、VEGFA、CASP3、IL-1β、JUN、PTGS2;KEGG通路富集分析PI3K-AKT信号通路、HIF-1信号通路等可能在止嗽散治疗慢性支气管炎中起关键作用;分子对接验证各核心靶点与其对应化合物之间均有较强的结合力。动物实验表明,与正常对照组比较,模型对照组大鼠血清、支气管肺泡灌洗液以及肺组织中IL-4、IL-6、TNF-α含量明显升高,肺组织PI3K、p-PI3K、AKT、p-AKT、HIF-1α、VEGFA蛋白表达明显上调(P<0.05或P<0.01);与模型对照组比较,止嗽散9.72 g/kg组、氢溴酸右美沙芬片8.1×10^(-3)g/kg组能明显改善肺组织病理变化,显著降低血清、支气管肺泡灌洗液以及肺组织中IL-4、IL-6、TNF-α含量,明显下调肺组织PI3K、p-PI3K、AKT、p-AKT、HIF-1α、VEGFA蛋白表达(P<0.05或P<0.01)。结论:止嗽散对慢性支气管炎模型大鼠具有较好的治疗作用,这可能与止嗽散中以槲皮素为代表的活性成分通过调控PI3K-AKT、HIF-1信号通路相关蛋白的表达抑制炎症反应有关。
Objective:To explore the mechanism of Zhisou Powder(止嗽散)in the treatment of chronic bronchitis through network pharmacology combined with animal experiments.Methods:The effective components,core targets and signaling pathways of Zhisou Powder in the treatment of chronic bronchitis were obtained using network pharmacology.The chronic bronchitis rat model was established,and the main targets and signaling pathways predicted by network pharmacology were verified by pathological staining,ELISA,immunohistochemistry,immunofluorescence and Western blot experiments.Results:The key effective components of Zhisou Powder selected by network pharmacology included quercetin,kaempferol,luteolin,β-sitosterol,7-methoxy-2-methyl isoflavone,nobiletin and formononetin,and the core targets involved TP53,TNF,IL-6,VEGFA,CASP3,IL-1β,JUN and PTGS2.KEGG pathway enrichment analysis revealed that PI3K-AKT and HIF-1 signaling pathways might play a key role in the treatment of chronic bronchitis.Molecular docking showed that there was strong binding between each core target and its corresponding compounds.Animal experiments demonstrated that compared with the conditions in the normal control group,the levels of IL-4,IL-6,TNF-αin serum,bronchoalveolar lavage fluid and lung tissue of rats in the model control group were increased,and the protein expression of PI3K,p-PI3K,AKT,p-AKT,HIF-1αand VEGFA in lung tissue was up-regulated(P<0.05 or P<0.01).Compared with the model control group,Zhisou Powder 9.72 g/kg group and dextromethorphan hydrobromide 8.1×10^(-3)g/kg group improved the pathological changes of lung tissue,reduced the levels of IL-4,IL-6 and TNF-αin serum,bronchoalveolar lavage fluid and lung tissue,and down-regulated the protein expression of PI3K,p-PI3K,AKT,p-AKT,HIF-1αand VEGFA in lung tissue(P<0.05 or P<0.01).Conclusion:Zhisou Powder had a good therapeutic effect on chronic bronchitis model rats,which might be related to the fact that the natural active components represented by quercetin in Zhisou Powder inhibit infl
作者
董娅慧
刘扬
杜佳慧
杨晔
刘园旭
尹登科
DONG Yahui;LIU Yang;DU Jiahui;YANG Ye;LIU Yuanxu;YIN Dengke(School of Pharmacy,Anhui University of Chinese Medicine,Hefei 230012;Anhui Key Laboratory of Research and Development of Chinese Medicine,Hefei 230012;Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application,Hefei 230012)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2023年第1期29-37,共9页
Pharmacology and Clinics of Chinese Materia Medica
基金
国家自然科学基金面上项目(编号:81874348)
安徽省高校学科(专业)拔尖人才学术资助项目(编号:gxbjZD2021056)
新安医学教育部重点实验室开放课题(编号:2020xayx11)。
关键词
止嗽散
慢性支气管炎
网络药理学
分子对接
作用机制
Zhisou Powder(止嗽散)
Chronic bronchitis
Network pharmacology
Molecular docking
Mechanism
