醒脑静注射液“异病同治”急性脑梗死与急性脑出血作用机制的网络药理学研究  

Mechanism of"Different Diseases with Same Treatment"with Xingnaojing Injection for the Treatment of Acute Cerebral Infarction and Acute Cerebral Hemorrhage Based on Network Pharmacology

作　　者：彭景 陈星[1] 吕秋艺 宋蕾 邹忆怀[1] PENG Jing;CHEN Xing;LYU Qiuyi;SONG Lei;ZOU Yihuai(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学东直门医院,北京100700 [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》2024年第2期231-238,共8页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金项目(No.81904285);北京市自然科学基金项目(No.7182104)。

摘　　要：目的:采用网络药理学探讨醒脑静注射液“异病同治”急性脑梗死(ACI)与急性脑出血(ACH)的作用机制。方法:利用中药系统药理学数据库及分析平台(TCMSP)与中医药综合数据库(TCMID)获得醒脑静注射液的有效成分及其作用靶点,同时利用人类基因数据库(GeneCards)、在线人类孟德尔遗传数据库(OMIM)、遗传药理学和药物基因组学数据库(PharmGkb)、治疗目标数据库(TTD)和药物靶标数据库(DrugBank)等数据库获取ACI和ACH潜在的基因靶点,在DIAGRAMS平台内绘制共同靶点韦恩图。采用Cytoscape 3.9软件构建醒脑静注射液“药物-活性成分-潜在靶点”相互作用网络图。利用STRING构建蛋白-蛋白相互作用(PPI)网络并进行拓扑分析。通过R/BioConductor对共同靶点进行基因本体(GO)及京都基因和基因组百科全书(KEGG)通路富集分析。结果:筛选共得到醒脑静注射液药物活性成分68种,对应靶点基因583个,ACI潜在靶点3 597个,ACH潜在靶点3 959个,三者共同靶点299个;PPI网络核心蛋白包括血管内皮生成因子A(VEGFA)、JUN转录因子(JUN)、信号转导与转录激活因子3(STAT3)、白细胞介素(IL)-6、肿瘤坏死因子(TNF)、清蛋白(ALB)、胱天蛋白酶3(CASP3)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、丝裂原活化蛋白激酶(MAPK)3、低氧诱导因子-1α(HIF-1α)、表皮生长因子受体(EGFR)、表皮生长因子(EGF)、前列腺素内过氧化物合酶2(PTGS2)、IL-1β、基质金属蛋白酶-9(MMP-9)等;其主要生物学通路涉及脂质与动脉粥样硬化、MAPK信号通路、流体剪切应力与动脉粥样硬化、TNF信号通路、凋亡、IL-17信号通路等。结论:醒脑静注射液通过抗氧化应激、抗炎症反应、抗细胞凋亡和促血管生成等作用机制达到“异病同治”ACI和ACH的疗效。Objective:To explore the mechanism of"different diseases with same treatment"of Xingnaojing injection for treating acute cerebral infarction(ACI)and acute cerebral hemorrhage(ACH)by network pharmacology.Methods:The effective components and the targets of Xingnaojing injection were obtained by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Traditional Chinese Medicine Integrated Database(TCMID).The potential gene targets of ACI and ACH were obtained by GeneCards,OMIM,PharmGkb,TTD,and DrugBank.The common target Venn diagram was drawn by DIAGRAMS.The interaction network of"drugs-active ingredients-potential targets"was constructed by Cytoscape 3.9 software.Finally,the protein-protein interaction(PPI)network was constructed by STRING and topology analysis was carried out.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment of common targets were analyzed by R/BioConductor.Results:There were 68 active components of Xingnaojing injection,583 corresponding target genes,of which 3597 potential targets were related to ACI,3959 potential targets were related to ACH,and there were 299 common targets.PPI network core proteins included vascular endothelial growth factor A(VEGFA),JUN,signal transducers and activators of transcription 3(STAT3),interleukin(IL)-6,tumor necrosis factors(TNF),serum albumin(ALB),caspase-3(CASP3),protein kinase(AKT)1,mitogen activated protein kinase(MAPK)3,hypoxia-inducible factor-1α(HIF-1α),epidermal growth factor receptor(EGFR),epidermal growth factor(EGF),recombinant prostaglandin endoperoxide synthase 2(PTGS2),IL-1β,matrix metalloproteinase 9(MMP-9);mainly pathway involved in lipid and arteriosclerosis,MAPK signal pathway,fluid shear stress and arteriosclerosis,TNF signal pathway,apoptosis,IL-17 signal pathway and so on.Conclusion:Xingnaojing injection achieves the therapeutic effect on ACI and ACH by anti-oxidative stress,anti-inflammatory reaction,anti-apoptosis,and promoting angiogenesis.

关 键 词：急性脑梗死 急性脑出血 醒脑静注射液 网络药理学 异病同治 

分 类 号：R285[医药卫生—中药学]