【摘要】 目的:应用网络药理学及分子对接技术探讨天麻降压胶囊治疗H型高血压病的作用机制,分析“清肝泻火,平肝潜阳”的现代科学内涵。方法:在多个数据库中筛选组方的中药有效成分及靶点,在多个数据库联合挖掘H型高血压病的治疗靶点基因,取二者的共有基因,应用Cytoscape构建疾病-有效成分-靶点的三元调控网络图,采用String数据库构建蛋白质-蛋白质相互作用网络,再采用Cytoscape软件筛选天麻降压胶囊治疗H型高血压病的核心基因,对共有靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析;最后利用AutoDock Tools、Vina及Pymol对有效成分与核心基因的分子对接。结果:筛选出天麻降压胶囊146个有效成分、312个靶点基因,与H型高血压病的交集靶点272个。GO富集分析获得天麻降压胶囊影响的生物过程2 876个,较为显著的过程有(细胞)对氧化应激的反应、对营养/氧气水平的反应,作用的细胞定位影响较大的有膜筏、膜微区、膜区域等,涉及的分子功能有256个,影响较大的有核受体的活动。结论:天麻降压胶囊可能主要通过多重中药组分共同作用于JUN、FOS、TNF等核心靶基因,降低机体氧化应激和炎症反应水平,并通过脂质和动脉粥样硬化通路、流体剪切应力和动脉粥样硬化通路及炎症反应通路减轻血管重塑,发挥治疗H型高血压病的作用,以达到中医“清肝泻火,平肝潜阳”之功效。更多还原

【Abstract】 Objective: To explore the action mechanism of the Tianma Antihypertensive capsules(天麻降压胶囊) on H-type hypertension by network pharmacology and molecular docking technology, and analyze the modern scientific connotation of “clearing away liver fire, and calming down liver Yang(阳)”. Methods: The active ingredients and targets of the prescpitions were screened in multiple databases, and the therapeutic target genes of H-type hypertension were jointly mined in multiple databases, and the common genes were selected. Cytoscape software was used to construct the ternary regulation network diagram of disease-active ingredient-target. String database was used to construct protein-protein interaction network, and then Cytoscape software was used to screen the core genes of the Tianma Antihypertensive capsules on H-type hypertension. The GO and KEGG enrichment analysis on the common targets was performed. Finally, AutoDock Tools, Vina and Pymol were used for molecular docking of active ingredients and core genes. Results: One hundred and forty-six active components and 312 target genes of the Tianma Antihypertensive capsules were screened, and 272 targets were intersected with H-type hypertension. The GO enrichment analysis showed that 2 876 biological processes were affected by the Tianma Antihypertensive capsules. The more significant biological processes were the response to oxidative stress and response to nutrition/oxygen levels. Membrane raft, membrane micro region, membrane region and so on had great influence on the cell localization. There were 256 molecular functions involved in the work, which affect the activities of nuclear receptors. Conclusions: The Tianma Antihypertensive capsules may reduce the levels of oxidative stress and inflammatory response in the body mainly through the combined effects of multiple Chinese materia medica components on the core target genes such as JUN, FOS, and TNF, and reduce vascular remodeling through lipid and atherosclerotic pathways, fluid shear stress, therosclerosis pathway and inflammatory response pathway to play the therapeutic role of treating H-type hypertension, so as to achieve the effect of “clearing away liver fire, and calming down liver Yang” in traditional Chinese medicine.更多还原