黄芩治疗主动脉夹层作用机制的预测及相关mRNA-miRNA-lncRNA网络构建

Prediction of Effect and Mechanism of Scutellaria baicalensis in Treatment of Aortic Dissection and Construction of Related mRNA-miRNA-lncRNA Network

目的通过网络药理学方法探究黄芩治疗主动脉夹层(AD)的作用机制及其调控的mRNA-miRNA-lncRNA网络构建.方法采用中药系统药理学数据库与分析平台(TCMSP)挖掘黄芩活性成分及预测靶点,通过挖掘GEO数据库,使用GEO2R分析筛选AD差异表达的mRNAs,运用StarBase v2.0、miRTarBase、Mircode在线分析软件进行mRNA-miRNA-lncRNA调控网络整合分析.借助Cytoscape 3.8.0软件与STRING数据库构建活性成分-靶点网络、三元转录网络及蛋白互作网络,并行GO功能及KEGG通路富集分析,最后予以分子对接评估.结果筛选出黄芩活性成分32个,其中23个靶点与AD相关.得到由11个关键mRNAs、27个关键miRNAs及340个关键lncRNAs构成的三元转录网络.富集分析结果显示,这些靶点主要通过IL-17、p53、TNF、FoxO和NOD样受体等信号通路发挥细胞增殖凋亡调控、转录调节、炎症反应和抗氧化活性作用.分子对接结果显示,汉黄芩素、β-谷甾醇、黄芩素和豆甾醇等主要活性成分均能与核心靶点IL6、MAPK14较好地结合.结论黄芩可能通过多组分、多靶点、多途径协同治疗AD,此结果可为进一步研究主动脉夹层作用机制提供理论依据.

Objective To explore the effect and mechanism of Scutellaria baicalensis in the treatment of aortic dissection(AD)and its regulated mRNA-miRNA-lncRNA network by network pharmacology.Method The active components and predicted targets of Scuaria baicalensis were mined by using the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform(TCMSP).The mRNAs differentially expressed in AD were screened by mining GEO database and GEO2R analysis.The mRNA-miRNA-lncRNA regulatory network integration analysis was performed by using StarBase v2.0,miRTarBase,and Mircode online analysis software.Cytoscape 3.8.0 software and STRING database were used to construct active component-target network,terpolymer transcription network and protein interaction network.GO function and KEGG pathway enrichment analysis were performed,and finally molecular docking assessment was performed.Results There were 32 active components of Scutellaria baicalensis,among which 23 targets were related to AD.mRNA-miRNA-lncRNA regulatory network consisting of 11 key mRNAs,27 key miRNAs and 340 key lncRNAs was obtained.Enrichment analysis showed that these targets play a role in cell proliferation and apoptosis regulation,transcriptional regulation,inflammatory response and antioxidant activity mainly through IL-17,p53,TNF,FoxO and NOD-like receptor signaling pathways.The results of molecular docking evaluation showed that the main active ingredients such as wogonin,β-sitosterol,baicalin and stigmasterol could combine well with the core target IL6 and MAPK14.Conclusion Scutellaria baicalensis may treat AD through multi-component,multi-target and multi-pathway collaboration,which can provide theoretical basis for further studying on the mechanism of aortic dissection.