基于网络药理学和分子对接探究川芎-丹参药对治疗心脑血管疾病的作用机制  

Study on the Mechanism of Drug Pair Ligusticum Chuanxiong-Salvia Miltiorrhiza in Treating Cardiac Cerebrovascular Diseases Based on Network Pharmacology and Molecular Docking

作　　者：白敏 刘烁[3] 张娟利 马阳 黄少杰 邹俊波 文爱东 史亚军[1] 丁一 Bai Min;Liu Shuo;Zhang Juanli;Ma Yang;Huang Shaojie;Zou Junbo;Wen Aidong;Shi Yajun;Ding Yi(School of Pharmacy,Shaanxi University of Traditional Chinese Medicine,Shaanxi Xianyang 712046,China;Department of Pharmacy,First Affiliated Hospital of Air Force Medical University;Jining Center for Disease Control and Prevention)

机构地区：[1]陕西中医药大学药学院,陕西咸阳712046 [2]空军军医大学第一附属医院药剂科 [3]济宁市疾病预防控制中心

出　　处：《中国药师》2022年第1期18-26,48,共10页China Pharmacist

基　　金：国家自然科学基金项目(编号:82074321);陕西省重点研究计划项目(编号:2021KW-56)。

摘　　要：目的:基于网络药理学和分子对接探究川芎-丹参药对治疗心脑血管疾病(CCVD)的作用机制。方法:采用中药系统药理学数据库分析平台(TCMSP)收集到川芎和丹参的成分,并与Gene Cards、OMIM、NCBI Gene数据库搜索CCVD的靶点取交集,用STRING数据库分析关键靶点间蛋白相互作用,利用Cytoscape3.7.1软件进行可视化,用DAVID数据库对相关潜在作用靶点进行基因本体(GO)分析及京都基因与基因组百科全书(KEGG)代谢通路富集分析,对潜在活性成分和关键靶点利用Autodock软件进行分子对接。最后通过检测细胞存活率、乳酸脱氢酶(LDH)释放相对抑制率及肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)含量对网络药理学和分子对接的结果进行验证。结果:共筛选出川芎-丹参药对有效成分49个和中药-疾病靶标78个,核心靶点涉及肿瘤蛋白P53(TP53)、原癌基因蛋白C-jun(JUN)、丝裂原活化蛋白激酶1(MAPK1)、肿瘤坏死因子(TNF)和信号转导与转录激活因子3(STAT3)等。GO功能富集分析得到375个GO条目,KEGG通路富集得到90条与CCVD密切相关的信号通路,其中包括神经活性配体-受体相互作用、缺氧诱导因子1(HIF-1)信号通路、TNF信号通路和雌激素信号通路等。分子对接结果显示川芎-丹参药对核心成分与CCVD关键靶点亲和力良好。体外验证实验表明川芎、丹参能有效提高HCM细胞的存活率,减少H/R损伤后LDH释放,并抑制HCM细胞的炎症反应、细胞凋亡等。结论:该研究预测了川芎-丹参药对的药效物质及作用机制,以期为其临床应用研究提供参考。Objective:To study the mechanism of Ligusticum chuanxiong-Salvia miltiorrhiza in the treatment of cardio-cerebro vascular disease(CCVD)based on network pharmacology and molecular docking.Methods:The components in Ligusticum chuanxiong and Salvia miltiorrhiza were collected using the Chinese Medicine System Pharmacology Database Analysis Platform(TCMSP);TCMSP,Gene Cards,OMIM and NCBI Gene database were used to search CCVD target intersection;STRING database was used to analyze protein interactions among key targets;Cytoscape 3.7.1 software was used to visualize;DAVID database was used to perform gene ontology(GO)analysis of related potential targets and Kyoto Encyclopedia of Genes and Genomes(KEGG)metabolic pathway enrichment analysis;Autodock software was used for molecular docking of potential active ingredients and key targets.The results of network pharmacology and molecular docking were verified by detecting cell survival rate,lactate dehydrogenase(LDH)relative release inhibition rate,and tumor necrosis factorα(TNF-α)and interleukin 6(IL-6)contents.Results:A total of 49 active components and 78 TCM disease targets were screened out,and the core targets involved TP53,Jun,MAPK1,TNF and STAT3,etc.GO functional enrichment analysis revealed 375 GO entries,and KEGG pathway enrichment revealed 90 signaling pathways closely related to CCVD,including neuroactive ligand receptor interaction,HIF-1 signaling pathway,TNF signaling pathway and estrogen signaling pathway,etc.Molecular docking results showed that Ligusticum chuanxiong-Salvia miltiorrhiza had a good affinity to the core components and the key targets of CCVD.In vitro validation experiments showed that Ligusticum chuanxiong and Salvia miltiorrhiza could effectively improve the survival rate of HCM cells,reduce the release of lactate dehydrogenase after H/R injury,and inhibit the inflammatory response and apoptosis of HCM cells.Conclusion:This study predicts the pharmacodynamic substances and action mechanism of Ligusticum chuanxiong-Salvia miltiorrhiza,which

关 键 词：心脑血管疾病 川芎 丹参 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]