四物汤治疗原发性高血压病的网络药理学机制探析  

Mechanism of Siwu Decoction(四物汤)in the Treatment of Hypertension Based on Network Pharmacology

作　　者：郇靖 彭思存[2] 樊毓运[2] HUAN Jing;PENG Sicun;FAN Yuyun(Guangzhou University of Chinese Medicine,Guangzhou 510065,Guangdong,China;Linyi People's Hospital,Linyi 276000,Shandong,China)

机构地区：[1]广州中医药大学,广东广州510065 [2]临沂市人民医院,山东临沂276000

出　　处：《实用中医内科杂志》2022年第6期82-85,I0008,I0009,共6页Journal of Practical Traditional Chinese Internal Medicine

基　　金：山东中医药科技发展计划项目(2019-0851,2017-464);齐鲁卫生与健康杰出青年人才项目(鲁卫人字〔2020〕3);临沂市科技发展计划项目(201919022,201717004);临沂人民医院博士创新基金(2016LYBS01);临沂市沂蒙中医优秀人才研修项目(临卫函〔2021〕7)。

摘　　要：目的基于网络药理学技术筛选四物汤治疗原发性高血压的作用靶点并探讨其可能的作用机制。方法从中药系统药理学数据库平台(TCMSP)收集当归、川芎、白芍、熟地黄的化学成分,并根据OB和DL值筛选活性成分并预测可能的作用靶点。从GENE CARDS数据库收集原发性高血压病的相关基因,并依托Cytoscape软件把药物—疾病—靶点可视化处理。将获得的关键靶基因采用STRING数据库构建PPI网络图,把关键靶点基因蛋白进行GO功能富集分析和KEGG通路富集分析。结果当归获得主要化学成分125个、川芎189个、白芍85个、熟地黄76个,筛去重复的靶点基因,获得15个有效活性成分和130个药物靶点蛋白,原发性高血压疾病相关基因2458个,药物与疾病共同的靶点基因45个。蛋白互作网络发现IL6、CASP3、JUK、PTGS2、ESR1等可能是四物汤治疗临床用于原发性高血压的关键靶点。GO富集分析确定了生物过程802个、分子功能100个、细胞组分58个(P<0.05),涉及蛋白质合成、酶的合成、类固醇等激素受体活性、蛋白质受体活性等各方面。KEGG通路富集分析获得134条相关信号通路,包括了细胞凋亡、调控炎性反应等方面,最代表性的有AGE-RAGE、IL-17等信号通路。结论本研究发现四物汤治疗原发性高血压病具有多途径、多靶点的特点,并尝试探讨了可能起作用关键靶点和涉及的可能的信号通路,为进一步的实验验证提供参考。Objective In this research,we used network pharmacology methods to choose the therapeutic targets of Siwu Decoc-tion(四物汤)in the treatment of hypertension(HTN)and explore the relevant mechanism.Methods The chemical components of Siwu Decoction including Danggui、Chuanxiong、Baishao、Shudi were collected through TCMSP to collect the effective active com-ponents and predict their targets.The genes of HTN were collected through Gene Cards,and the Cytoscape software was used to describe networks of drug-targets and disease-targets.These key genes were uploaded to the online STRING database to ana-lyze and construct PPI networks,and then perform GO functional enrichment analysis and KEGG pathway enrichment analysis a-bout those key target proteins.Results We got a total of 125 major chemical components of Danggui,189 of Chuanxiong,85 of Baishao,and 76 of Shudi,a total of 15 active ingredients and 130 target proteins after removal of duplicates.There were2458 genes related of HTN and 45 common targets between drug and disease.The network of the protein interaction found that IL6、CASP3、JUK、PTGS2 and ESR1 might be the key targets of Siwu Decoction in the treatment for HTN.The GO enrichment analysis identified the items of 802 biologial processes,100 molecular functions,58 cellular components(P<0.05),involving protein binding,enzyme binding,steroid hormone receptor activity,adrenergic receptor activity and other aspects.The KEGG pathway enrichment identified 134 signal pathways,involving inflammation,anti-cancer,apoptosis,endocrine,and others,including AGE-RAGE、IL-17 and other signal pathways.Conclusion The siwu decoction has the characteristics of multi-pathway and multi-target action in the treatment of the hypertension.The key targets,biological processes and signal pathways involved were revealed in this study,which provided a reference and basis for further research.

关 键 词：四物汤 原发性高血压病 网络药理学 靶点 通路 

分 类 号：R285[医药卫生—中药学]