基于网络药理学和动物实验探讨扶脉益心汤治疗冠脉微循环疾病的作用机制

The mechanism of Fumai Yixin decoction in the treatment of coronary microcirculation dis⁃ease based on network pharmacology and animal experiments

目的:基于网络药理学和动物实验探讨扶脉益心汤治疗冠脉微循环疾病(CMD)的作用机制。方法:在中药系统药理学分析平台(TCMSP)及文献等筛选扶脉益心汤的活性成分及药物靶点,通过GeneCard等数据库检索CMD靶点,通过韦恩图得到药物和疾病的共同靶点,构建蛋白质相互作用(PPI)网络图,将共同靶点进行基因本体(GO)、KEGG通路富集分析,分子对接技术展示成分和靶点结合力。构建大鼠疾病模型,荧光定量法检测心肌组织中白介素6(IL-6)、白介素8(IL-8)、血管内皮生长因子A(VEGFA)、丝裂原活化蛋白激酶3(MAPK3)等mRNA表达水平。结果:通过TCMSP等数据库及文献得到活成分25个,通过韦恩图得到药物-疾病共同靶点156个,PPI网络相互作用紧密,关键通路涉及PI3K-Akt信号通路、VEGF信号通路。分子对接结果显示成分与靶点具有较好的结合力。荧光定量结果显示:与空白组相比,模型组(CMD组)IL-6、IL-8、MAPK3等mRNA表达水平升高,VEGFAmRNA表达水平下降;与模型组相比,扶脉益心汤组(高剂量组)IL-6、IL-8、MAPK3等mRNA表达水平下降,VEGFAmRNA表达水平升高(P<0.05或P<0.01)。结论:扶脉益心汤可通过作用于炎症、血管内皮等相关的靶点和通路治疗CMD,为以后扶脉益心汤的临床应用提供了理论基础。

Objective:To explore the mechanism of Fumai Yixin decoction in the treatment of coronary microcirculation disease(CMD)based on network pharmacology and animal experiments.Methods:The active components and drug targets of Fumai Yixin decoction were screened on the Chinese Medicine System Pharmacology Analysis Platform(TCMSP)and literature,and the CMD targets were retrieved from databases such as Gene-Card.The common targets of drugs and diseases were obtained from Venn diagram,and a protein-protein interaction(PPI)network diagram was constructed.The enrichment analysis of gene ontology(GO)and KEGG pathways were performed on the common targets,and the component and target binding forces were displayed by molecular docking technology.The rat disease model was constructed,and the mRNA expression levels of interleukin-6(IL-6),interleukin-8(IL-8),vascular endothelial growth factor(VEGFA),and mitogen-activated protein kinase 3(MAPK3)in the myocardial tissue were detected by RT-qPCR.Results:Twenty-five active components were obtained from databases such as TCMSP and relevant literature,and 156 drug-disease common targets were obtained from Venn diagram.The interaction of PPI networks was close,and the key pathways involved PI3KAkt signaling pathway and VEGF signaling pathway.Molecular docking results showed that the components had good binding capacity to the target.RT-qPCR results showed that compared with the blank group,the mRNA expression levels of IL-6,IL-8,and MAPK3 in the model group(CMD group)were increased,while the expression level of VEGFAmRNA was decreased.Compared with the model group,the mRNA expression levels of IL-6,IL-8,and MAPK3 in the Fumai Yixin decoction group(high dose group)were decreased,whereas the expression level of VEGFAmRNA was increased(P<0.05 or P<0.01).Conclusion:Fumai Yixin decoction can treat CMD by acting on the inflammation,vascular endothelial and other related targets and pathways,which provides a theoretical basis for the clinical application of Fumai Yixin decoction in the future.