基于网络药理学探讨丹参饮治疗扩张型心肌病的作用机制  

Mechanism of Danshen Decoction in Treating Dilated Cardiomyopathy Based on Network Pharmacology

作　　者：何轩辉 陈恒文[1] 谭雨晴 HE Xuanhui;CHEN Hengwen;TAN Yuqing(Guang′anmen Hospital,China Academy of Chinese Medicine Science,Beijing 100053,China)

机构地区：[1]中国中医科学院广安门医院,北京100053 [2]北京中医药大学,北京100029

出　　处：《中西医结合心脑血管病杂志》2022年第5期791-800,共10页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金项目(No.82074396)。

摘　　要：目的采用网络药理学研究方法分析丹参饮治疗扩张型心肌病的药物作用机制。方法检索中药系统药理学技术平台(TCMSP)数据库,筛选丹参、降香、砂仁3味药物的主要活性成分并检索其作用靶点,基于GeneCards和OMIM数据库查询与扩张型心肌病相关的靶点。应用Cytoscape 3.7.2软件构建“丹参饮-成分-作用靶点”网络图,寻找丹参饮药物靶点与扩张型心肌病疾病靶点重复值,运用STRING构建蛋白相互作用(PPI)网络,采用DAVID平台进行生物学功能及通路富集分析。结果筛选得到丹参饮有效活性成分112个,关键作用成分为β-谷甾醇、木犀草素、丹参酮ⅡA、维斯体素、柚皮素等,药物相应靶点151个,扩张型心肌病相关靶点891个,最终获取交集靶点44个,网络图中核心位置的靶点包括钠通道蛋白5型亚基α(SCN5A)、β2-肾上腺素能受体(ADRB2)、雌激素受体(ESR1)、诱导型一氧化氮合酶(NOS2)、过氧化物酶体增殖物激活受体γ(PPARG)等。富集分析显示,主要通过RNA聚合酶Ⅱ启动子转录正向调控、药物反应、凋亡过程的负调控等生物学过程干预扩张型心肌病,且具有蛋白质结合、细胞因子活性、蛋白质异二聚化活性等分子功能。丹参饮可能通过肿瘤坏死因子(TNF)信号通路、磷脂酰肌醇3-激酶(PI3K)-磷酸激酶B(Akt)信号通路、低氧诱导因子-1(HIF-1)信号通路、钙信号通路等达到治疗扩张型心肌病的效果。结论初步筛选丹参饮治疗扩张型心肌病的作用靶点和复杂通路,为后续深入研究中医药治疗扩张型心肌病的药物机制研究提供参考。Objective To analyze the mechanism of Danshen Decoction in the treatment of dilated cardiomyopathy by network pharmacology.Methods Traditional Chinese Medicines Systems Pharmacology Platform(TCMSP)database was searched to screen the main active components and targets of Salvia miltiorrhiza,Dalbergia odorifera,and Amomum.The targets related to dilated cardiomyopathy were searched based on the Genecards and OMIM databases.Cytoscape 3.7.2 software was used to construct the network diagram of"Danshenyin-components-targets of action"to find the duplicate values of the targets.Protein interaction network was constructed using STRING,and DAVID platform was used for biological function and pathway enrichment analysis.Results One hundred and twelve effective active components with 151 targets of Danshen Decoction were screened,the key components wereβ-sitosterol,luteolin,tanshinoneⅡA,Vestitol,and naringenin.Eight hundred and ninety-one disease-related targets and 44 intersection targets were obtained.The core positions in the target network diagram were voltage-gated sodium channelα5-subunit(SCN5A),β2-drenergic receptor(ADRB2),estrogen receptor 1(ESR1),nitric oxide synthase 2(NOS2),and peroxisome proliferator activated receptorγ(PPARG),etc.Enrichment analysis showed that dilated cardiomyopathy was mainly intervened by biological processes such as positive regulation of transcription from RNA polymeraseⅡpromoter,response to drug,and negative regulation of apoptotic process.The molecular functions of Danshen Decoction regulating dilated cardiomyopathy were mainly concentrated in protein binding,cytokine activity,and protein heterodimerization activity.Danshen Decoction could achieve the effect of treating dilated cardiomyopathy through tumor necrosis factor(TNF)signaling pathway,phosphatidylinositol 3-kinases(PI3K)-protein kinase B(Akt)signaling pathway,hypoxia-inducible factor-1(HIF-1)signaling pathway,and calcium signaling pathway.Conclusion This study preliminarily screened the targets and complex pathways of Dan

关 键 词：扩张型心肌病 丹参饮 网络药理学 作用机制 

分 类 号：R54[医药卫生—心血管疾病]