基于网络药理学探究槲寄生-黄芪治疗老年高血压病的作用机制

A study on the action mechanism of Hujisheng-Huangqi paired medicines on senile hypertension based on network pharmacology

背景:高血压是多种心血管疾病的重要风险因子之一,我国老年高血压病存在患病率高、控制率低的特点。益肾降压方为临床治疗老年高血压病的有效方剂,槲寄生与黄芪药对是组方的精髓,但其作用机制尚不明确。网络药理学能够阐明药理作用机制、寻找药效物质基础和潜在靶点。目的:基于网络药理学方法探究益肾降压方中槲寄生-黄芪药对治疗老年高血压病的作用机制。方法:检索TCMSP数据库,筛选槲寄生、黄芪的活性成分及靶点,利用UniProt数据库对靶点信息进行标准化,通过GeneCards数据库获取老年高血压病相关疾病靶点,在Venny 2.1.0在线平台上制作韦恩图,获得槲寄生、黄芪与疾病的共同靶点,通过Cytoscape软件构建药物-活性化合物-靶点-疾病网络,通过STRING数据库构建蛋白质-蛋白质相互作用网络,利用DAVID数据库对交集靶点进行富集分析。结果:筛选得到槲寄生-黄芪药对治疗老年高血压病的核心成分为槲皮素、异鼠李素、刺芒柄花素、β-谷甾醇、山柰酚等,核心靶点包括白细胞介素(Interleukin,IL)-6、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、丝氨酸/苏氨酸蛋白激酶1(AKT Serine/Threonine Kinase 1,AKT1)、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)、基质金属蛋白酶9(Matrix Metalloproteinase 9,MMP9)等,主要通路有脂质和动脉粥样硬化、流体剪切应力和动脉粥样硬化、核因子-κB(Nuclear Factor-κB,NF-κB)信号通路、丝裂原活化蛋白激酶(Mitogen-activated Protein Kinase,MAPK)信号通路、磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)信号通路、Toll样受体信号通路等。结论:槲寄生、黄芪可以通过多成分、多靶点、多通路发挥治疗老年高血压病的作用,为临床继续深入研究老年高血压病的机制提供了思路与线索。

Background:Hypertension is one of the important risk factors of various cardiovascular diseases.Senile hypertension in China has the characteristics of high prevalence and low control rate.The Yishen Jiangya prescription(益肾降压方)is an effective prescription for the clinical treatment of senile hypertension.Hujisheng(Herba Visci)-Huangqi(Radix Astragali)pairedB medicines are the essence of the prescription,but its action mechanism is still unclear.Network pharmacology can elucidate pharmacological mechanisms,identify pharmacological substance bases and potential targets.Objective:To explore the action mechanism of Hujisheng-Huangqi paired medicines on senile hypertension based on network pharmacology.Methods:The data was retrieved in TCMSP database to screen the active components and targets of Hujisheng and Huangqi.The target information was standardized by UniProt database.The targets of senile hypertension were obtained by GeneCards database.The intersection targets of Hujisheng-Huangqi paired medicines and disease were obtained by making Venny map by Venny 2.1.0 online platform.The network of medicine-active compounds-targets-disease was constructed by Cytoscape software,and the PPI network was constructed through STRING database.DAVID database was used to perform the enrichment analysis of intersection targets.Results:The core components of Hujisheng-Huangqi paired medicines on senile hypertension were screened,including quercetin,isorhamnetin,monononin,β-sitosterol,kaempferol,etc..Core targets were IL-6,TNF,AKT1,VEGFA,MMP9,etc..The main pathways included lipid and atherosclerosis,fluid shear stress and atherosclerosis,NF-κB signaling pathway,MAPK signaling pathway,PI3K-Akt signaling pathway,Toll-like receptor signaling pathway,etc..Conclusion:Hujisheng-Huangqi paired medicines can play a role in the treatment of senile hypertension through multiple components,multiple targets and multiple pathways,which provides ideas and clues for further clinical research on the mechanism of senile hypertension.