基于网络药理学及实验验证探讨罗布麻叶-钩藤药对治疗高血压病的作用机制  

Mechanism of Apocyni Veneti Folium-Uncariae Ramulus Cum Uncis in Treating Hypertension Based on Network Pharmacology and Experimental Verification

作　　者：李东娜 司香环 李宏佳 徐天舒[1,2] LI Dongna;SI Xianghuan;LI Hongjia;XU Tianshu(Gulou Clinical Medical School of Nanjing University of Chinese Medicine,Nanjing Jiangsu 210008,China;Department of Chinese Medicine,The Affiliated Drum Tower Hospital of Nanjing University Medical School,Nanjing Jiangsu 210008,China)

机构地区：[1]南京中医药大学鼓楼临床医学院,江苏南京210008 [2]南京大学附属鼓楼医院中医科,江苏南京210008

出　　处：《新中医》2024年第2期177-185,共9页New Chinese Medicine

基　　金：国家自然科学基金面上项目(82273907);江苏省中医药科技发展计划项目(YB201938)。

摘　　要：目的:利用网络药理学及实验验证的方法探讨罗布麻叶-钩藤药对治疗高血压病的作用机制。方法:使用中药系统药理学数据库与分析平台(TCMSP)数据库,筛选罗布麻叶-钩藤主要化学成分和作用靶点,高血压病疾病靶点通过GeneCards、在线人类孟德尔遗传数据库(OMIM)查询,将罗布麻叶-钩藤的作用靶点与疾病靶点交集得到罗布麻叶-钩藤药对治疗高血压病的共同靶点,将共同靶点导入STRING数据库构建蛋白-蛋白相互作用(PPI)网络。将共同靶点导入DAVID在线数据库进行基因本体(GO)与京都基因与基因组百科全书(KEGG)富集分析,使用AutoDock和PyMOL进行分子对接和可视化。采用两肾一夹法建立高血压病大鼠模型,治疗组大鼠给予罗布麻叶-钩藤药液连续灌胃2周,模型组与空白组给予等体积0.9%氯化钠溶液连续灌胃2周。比较3组收缩压(SBP)、胸主动脉病理结构及炎症指标水平。结果:筛选后得出罗布麻叶的活性成分6个,钩藤的活性成分33个,罗布麻叶-钩藤药对治疗高血压病的靶点152个,包括肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-1β、IL-8、IL-4、IL-1α、IL-2、IL-10、趋化因子配体2 (CCL2)、细胞间黏附分子-1 (ICAM1)等。KEGG富集分析共得到TNF信号通路、缺氧诱导因子-1 (HIF-1)信号通路、Toll样受体(TRL)信号通路等122条信号通路。分子对接结果显示,山柰酚和槲皮素与TNF、CCL2和IL-8等结合较好。实验结果显示罗布麻叶-钩藤药对显著降低了高血压病大鼠的血压,有效改善了高血压病大鼠胸主动脉的病理组织结构,降低了高血压病大鼠血清IL-6、IL-10、IL-1β、TNF-α水平。结论:罗布麻叶-钩藤药对可通过多成分、多靶点、多通路治疗高血压病。Objective:To explore the mechanism of Apocyni Veneti Folium-Uncariae Ramulus Cum Uncis in treating hypertension based on network pharmacology and experimental verification.Methods:The main chemical components and action targets of Apocyni Veneti Folium-Uncariae Ramulus Cum Uncis were screened by Traditional Chinese Medicine Systems Pharmacology Platform(TCMSP).The targets of hypertension were investigated by Gene Cards and Online Mendelian Inheritance in Man(OMIM).The common targets for treating hypertension were obtained by intersecting the action targets of Apocyni Veneti Folium-Uncariae Ramulus Cum Uncis and the disease targets.The common targets were imported into the STRING database to construct the protein-protein interaction(PPI) network.The common targets were imported into the DAVID online database for gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis,and AutoDock and PyMOL were used for molecular docking and visualization.Model rats with hypertension were established by two-kidney and one-clip method.The rats in the treatment group were given solution of Apocyni Veneti Folium-Uncariae Ramulus Cum Uncis by gavage for two weeks,and the rats in the model group and the blank group were given 0.9% sodium chloride solution by gavage for two weeks.The systolic blood pressure(SBP),pathological structure of thoracic aorta and inflammatory indexes were compared between the three groups.Results:After screening,6 active components of Apocyni Veneti Folium,33 active components of Uncariae Ramulus Cum Uncis,and 152 targets of Apocyni Veneti Folium-Uncariae Ramulus Cum Uncis in treating hypertension were obtained,including tumor necrosis factor(TNF)-α,interleukin(IL)-6,IL-1β,IL-8,IL-4,IL-1α,IL-2,IL-10,chemokine C-C motif ligand 2(CCL2) and intercellular cell adhesion molecule-1(ICAM1).A total of 122 signaling pathways including TNF signaling pathway,hypoxia-inducible factor-1(HIF-1)signaling pathway and Toll-like receptor(TRL) signaling pathway were obtained by KEGG enrichment

关 键 词：高血压病 罗布麻叶 钩藤 作用机制 网络药理学 实验验证 

分 类 号：R285[医药卫生—中药学]