基于网络药理学探讨加味参附颗粒治疗慢性心力衰竭的潜在靶点及作用机制  

Exploring the Potential Targets and Mechanism of Action of Modified Shenfu Granules in the Treatment of Chronic Heart Failure Based on Network Pharmacology

作　　者：叶润杰 黄培红[2] YE Run-Jie;HUANG Pei-Hong(Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong,China;Guangdong Second Traditional Chinese Medicine Hospital,Guangzhou 510095 Guangdong,China)

机构地区：[1]广州中医药大学,广东广州510006 [2]广东省第二中医院,广东广州510095

出　　处：《广州中医药大学学报》2023年第11期2867-2876,共10页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：广东省财政厅“中医特色重点医院建设工程”项目(粤财社【2023】139号)。

摘　　要：【目的】利用网络药理学预测加味参附颗粒治疗慢性心力衰竭(CHF)的潜在靶点及其作用机制。【方法】通过TCMSP和BATMAN数据库获取加味参附颗粒的相关活性成分和靶点,通过GeneCards、DisGeNET数据库遴选慢性心力衰竭相关的靶点,取交集靶点;运用STRING数据库进行靶蛋白互作分析。运用Metascape数据库对药物-疾病共同靶点进行基因本体论(GO)和京都基因与基因百科全书(KEGG)富集分析。运用Cytoscape 3.9.1软件构建成分-靶点-通路网络图。【结果】筛选出加味参附颗粒中42个活性成分和435个直接作用的蛋白靶点,得到38个药物-疾病交集靶点。GO与KEGG富集分析结果显示,加味参附颗粒在血液循环、清除氧自由基、平滑肌细胞的调节、细胞和基因调控等多生物过程方面,通过IL-6、RELA、TNF、VEGFA、MMP-2、MAPK8、TP53、EDN1、MMP-9等核心靶点,流体剪切应力与动脉粥样硬化途径、AGERAGE、HIF-1、MAPK、IL-17、TNF、cAMP、钙等信号通路治疗慢性心力衰竭。【结论】加味参附颗粒可通过改善心脏供血、抑制炎症反应、抗氧化应激、抑制心肌重构、调节心肌细胞的代谢等方面多靶点多途径治疗慢性心力衰竭。Objective To predict the potential targets and their mechanisms of action of Modified Shenfu Granules in treating chronic heart failure(CHF)using Network pharmacology.Methods The TCMSP and BATMAN databases were used to obtain the relevant active components and targets of Modified Shenfu Granules,the GeneCards and DisGeNET databases were used to select the targets related to CHF,and then the intersection targets were obtained;the STRING database was used to analyze the interactions of target proteins.Gene ontology(GO)and Kyoto Encyclopedia of Genes and genomes(KEGG)enrichment analyses of drug-disease common targets were performed using the Metascape database.Component-target-pathway network map was constructed using Cytoscape 3.9.1 software.Results A total of 42 active components and 435 direct-acting protein targets were screened in Modified Shenfu Granules,and 38 drug-disease intersection targets were obtained.GO and KEGG enrichment analyses showed that Modified Shenfu Granules had multi-biological aspects in blood circulation,scavenging of oxygen free radicals,regulation of smooth muscle cells,and cellular and gene regulation,through IL-6,RELA,TNF,VEGFA,and MMP-2,MAPK8,TP53,EDN1,MMP-9 and other core targets,and fluid shear stress and atherosclerosis pathway,AGE-RAGE,HIF-1,MAPK,IL-17,TNF,cAMP,calcium and other signaling pathways to treat CHF.Conclusion Modified Shenfu Granules can treat CHF by a multi-target multi-channel approach through improving cardiac blood supply,inhibiting inflammatory response,antioxidative stress,inhibiting cardiac remodeling,and regulating the metabolism of cardiomyocytes.

关 键 词：加味参附颗粒 慢性心力衰竭 网络药理学 潜在靶点 作用机制 

分 类 号：R285.5[医药卫生—中药学]