基于网络药理学的丹参-红花治疗心肌梗死的作用及其机制研究  

Effect and mechanism of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos on myocardial infarction based on network pharmacology

作　　者：卜雕雕 苏卓 柏希慧 张丹[1] 王昌利[1] BU Diao-diao;SU Zhuo;BAI Xi-hui;ZHANG Dan;WANG Chang-li(College of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang 712046,China;School of Pharmacy,Xi’an Jiaotong University,Xi’an 710049,China)

机构地区：[1]陕西中医药大学药学院,陕西咸阳712046 [2]西安交通大学药学院,陕西西安710049

出　　处：《中草药》2020年第10期2807-2818,共12页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金项目(81373944)。

摘　　要：目的运用网络药理学和实验验证的方法探究丹参-红花治疗心肌梗死(MI)的作用机制。方法通过中医药系统药理学数据库和分析平台(TCMSP)检索丹参、红花的主要成分,并通过TCMSP和Swiss Target prediction数据库筛选成分靶点,结合OMIM、TTD、Genecards和NCBI(Gene)数据库获取丹参-红花治疗MI的作用靶点。应用STRING平台构建蛋白-蛋白相互作用(PPI)网络模型。应用DAVID软件进行基因本体(GO)富集分析和KEGG通路富集分析,Cytoscape构建药材-靶点和药材-成分-靶点-通路网络图,进一步进行实验验证,以揭示丹参-红花对小鼠MI的治疗作用。结果筛选得到84个活性成分,检索出485个靶蛋白,与MI有关的靶点有28个。GO功能富集分析得到GO条目18个(P<0.05),其中生物过程(BP)条目9个、分子功能(CC)条目3个、细胞组成(MF)条目6个。KEGG通路富集筛选得到30条信号通路(P<0.05),涉及缺氧诱导因子信号通路以及肿瘤坏死因子、血管内皮生长因子、鞘磷脂类、小G蛋白Rap1等与MI相关的信号通路。HE染色和Masson染色结果显示,丹参-红花不同剂量组能明显改善心肌损伤,Western blotting结果显示,丹参-红花能下调肿瘤坏死因子-α(TNF-α)和有丝分裂原活化蛋白激酶(MAPK)表达来改善心肌损伤。结论应用网络药理学方法阐释了丹参-红花治疗MI的作用靶点及通路,为后续深入阐明丹参-红花治疗MI提供科学依据。Objective To study the mechanism of Salviae Miltiorrhizae Radix(SMR) et Rhizoma and Carthamii Flos(CF) in the treatment of myocardial infarction(MI) by means of network pharmacology and experimental verification. Methods The main components of SMR-CF were searched by Traditional Chinese Medicine System Pharmacological Analysis Platform(TCMSP), and the component targets were screened by TCMSP and Swiss Target prediction databases, and the MI related targets were queried through OMIM, TTD, Genecards and NCBI(Gene) databases. The common target proteins of disease and drug components were screened by the intersection of drug targets and disease targets. The network model of protein-protein interaction(PPI) was constructed by using STRING platform. The functional enrichment analysis of gene ontology(GO) and the KEGG pathway were carried out by using DAVID. Cytoscape was used to construct medicinal material-target and medicinal material-composition-target-pathway network map for further experimental verification, in order to reveal the therapeutic effect of SMR-CF on MI in mice. Results A total of 84 active components were screened from SMR and CF, 485 target proteins were searched, and 28 targets related to MI were found. GO functional enrichment analysis showed that there were 18 GO entries, including 9 biological process(BP) entries, three molecular functional(MF) entries and six cell composition(CC) entries. KEGG pathway was enriched and screened to obtain 30 signal pathways, such as hypoxia inducible factor signaling pathway, tumor necrosis factor, vascular endothelial growth factor, sheath phospholipid, small G protein Rap1 and so on. The results of HE staining and Masson staining showed that SMR-CF could significantly improve myocardial injury. Western blotting results showed that SMR-CF could down-regulate the expression of TNF-α and MAPK to improve myocardial injury. Conclusion The target and pathway of SMR-CF in the treatment of MI are explained by network pharmacology, which provides a scientific basis for

关 键 词：丹参 红花 心肌梗死 网络药理学 缺氧诱导因子信号通路 肿瘤坏死因子 血管内皮生长因子 鞘磷脂类 小G蛋白Rap1 肿瘤坏死因子-α(TNF-α) 有丝分裂原活化蛋白激酶(MAPK) 

分 类 号：R285.5[医药卫生—中药学]