基于GEO芯片及网络药理学探讨夏桑菊颗粒治疗高血压病的机制研究

Study on the therapeutic mechanism of Xiasangju Granule against hypertension based on GEO chip and network pharmacology

关键词:  夏桑菊颗粒|高血压病|GEO芯片|网络药理学|分子对接

Key words:  Xiasangju Granule|hypertension|GEO chip|network pharmacology|molecular docking

摘要:

[目的] 基于基因表达汇编（GEO）芯片、网络药理学及分子对接技术探讨夏桑菊颗粒治疗高血压病的作用机制。[方法] 利用TCMSP数据库获取和筛选夏桑菊颗粒的活性成分及成分靶点构建“中药-化合物-靶点”网络；利用GEO芯片技术、GeneCards、OMIM、TTD数据库获取并筛选高血压病的疾病靶点；将成分靶点与疾病靶点取交集靶点构建蛋白质-蛋白质相互作用（PPI）网络，两次处理筛选关键靶点；对交集靶点进行基因本体（GO）及京都基因与基因组百科全书（KEGG）富集分析；将关键靶点前4位与其对应活性成分进行分子对接分析。[结果] 获得成分靶点194个、疾病靶点2 168个、交集靶点126个、关键靶点6个；GO和KEGG富集分析显示夏桑菊颗粒主要与对激素、无机物、氮化合物、脂多糖、细胞外刺激等的反应等生物过程有关，主要富集通路涉及脂质与动脉粥样硬化、晚期糖基化产物-晚期糖基化终末产物受体（AGE-RAGE）、磷酸酰肌醇3-激酶-丝苏氨酸蛋白激酶（PI3K-AKT）、丝裂原活化蛋白激酶（MAPK）、肿瘤坏死因子（TNF）等信号通路；分子对接结果显示关键靶点与活性成分结合良好。[结论] 夏桑菊颗粒可通过多成分-多靶点-多途径发挥作用，为其防治高血压病临床使用提供了一定的参考依据。

Abstract:

[Objective] To explore the therapeutic mechanism of Xiasangju Granules against hypertension based on GEO chip,network pharmacology,and molecular docking.[Methods] TCMSP database was used to obtain and screen the active components and component targets of Xiasangju Granules,and the "herb-compound-target" network was constructed. Using GEO chip technology,Genecards,OMIM, and TTD databases to obtain and screen the disease targets of hypertension. The intersection targets were taken and the "herb-compound-target" network was constructed. Take the intersection target of component target and disease target,construct PPI network,and screen the key target by secondary processing. Go and KEGG enrichment analysis of intersection targets. The first four positions of key targets and their corresponding active components were analyzed by molecular docking.[Results] The 194 component targets,2 168 disease targets,126 intersection targets,and 6 key targets were obtained. Go and KEGG enrichment analysis showed that Xiasangju Granules were mainly related to biological processes such as response to hormones,inorganic substances,nitrogen compounds,lipopolysaccharide,and extracellular stimulation. The main enrichment pathways involved signal pathways such as lipid and atherosclerosis,AGE-RAGE,PI3K-Akt,MAPK and TNF. The results of molecular docking showed that the key targets were well combined with the active components.[Conclusion] Xiasangju Granules can exert an effect through multi-component,multi-target,and multi-channel,which provides a reference for its clinical use in the prevention and treatment of hypertension.