基于多种网络药理平台探讨小陷胸汤治疗高血压的作用机制

目的：基于网络药理学方法探讨小陷胸汤治疗高血压的作用机制。方法：通过SymMap、TCMSP、DrugBank 3个数据库获得小陷胸汤的有效成分及其靶点；并与TCMSP、TCMIP、DrugBank 3个数据库收集的高血压的靶点进行比对，获得小陷胸汤作用于高血压的靶点。运用David数据库对小陷胸汤和高血压共同作用靶点蛋白进行GO富集分析和KEGG通路富集分析；运用STRING数据库得到小陷胸汤作用于高血压的PPI网络；运用Cytoscape对PPI网络进行拓扑分析得到关键靶点。结果：小陷胸汤作用于高血压的有效成分有33个，相关靶点48个，关键靶点基因14个。GO富集分析显示，小陷胸汤治疗高血压的生物过程显著富集在对非生物刺激的反应、毒蕈碱型乙酰胆碱受体信号通路、系统过程的调节、第二信使介导的信号、细胞增殖等；细胞组分主要富集在轴突、质膜部分、不对称突触、神经末梢、神经元投射、突触后膜、细胞外基质等；分子功能主要富集在胺受体活性、肾上腺素受体活性、毒蕈碱乙酰胆碱受体活性、G蛋白偶联的乙酰胆碱受体活性、α-肾上腺素受体活性等；KEGG通路富集显示小陷胸汤治疗高血压影响的通路主要有神经活性配体-受体相互作用、钙信号通路、血管平滑肌收缩、肌动蛋白细胞骨架的调节、色氨酸代谢等。结论：小陷胸汤治疗高血压的机制可能是通过小陷胸汤黄连的成分槲皮素、小檗碱、R-氢化小檗碱，半夏的成分卡文定碱、豆甾醇、松柏苷和瓜蒌的成分菠菜甾醇等达到抗炎抗氧化应激，改善内皮功能等作用，通过调节相关靶蛋白的基因表达，调控血管组织重构与细胞外基质代谢，减轻炎性反应，参与神经活性配体-受体相互作用、钙信号通路、血管平滑肌收缩等通路来降低血压。

Multiple Network Pharmacological Platforms-Based Mechanism of Xiaoxianxiong Decoction in Treatment of Hypertension

To explore the mechanism of Xiaoxianxiong Decoction in treating of hypertension based on network pharmacology.Methods:The effective chemical constituents and targets of Xiaoxianxiong Decoction were obtained from three databases:SymMap,TCMSP,DrugBank.The targets of hypertension collected by TCMSP,TCMIP and DrugBank databases were compared to the targets of Xiaoxianxiong Decoction to obtain the targets of Xiaoxianxiong Decoction in treating of hypertension.The David database was used to analyze the GO and KEGG pathway enrichment analysis of the mutual target proteins of Xiaoxianxiong Decoction and hypertension.The STRING database was used to construct the PPI network of Xiaoxianxiong Decoction in treating of hypertension.The Cytoscape was used to perform the topological analysis of the PPI network to obtain the key targets.Results:There were 33 active components of Xiaoxianxiong Decoction in treatment of hypertension,48 related targets and 14 key target genes.GO enrichment analysis showed that the biological processes of Xiaoxianxiong Decoction in treatment of hypertension were significantly enriched on the response to abiotic stimulus,muscarinic acetylcholine receptor signaling pathway,regulation of systemic processes,second-messenger-mediated signaling,and cell proliferation etc.Cell components were mainly concentrated on axons,plasma membrane part,asymmetric synapse,nerve terminal,neuron projection,postsynaptic membrane,extracellular matrix etc.Molecular functions were mainly concentrated on amine receptor activity,adrenoceptor activity,muscarinic acetylcholine receptor activity,G-protein coupled acetylcholine receptor activity,alpha-adrenergic receptor activity etc.KEGG pathway enrichment analysis showed that affected pathways included neuroactive ligand-receptor interaction,calcium signaling pathway,vascular smooth muscle contraction,regulation of actin cytoskeleton,tryptophan metabolism etc.Conclusion:The mechanism of Xiaoxianxiong Decoction in treating hypertension may resist inflammatory and oxidative stress and improve endothelial function by quercetin,berberine,R-Hydrogenated berberine of golden thread,cavidine,stigmasterol,coniferin of pinellia tuber and spinasterol of snakegourd fruit,etc.The mechanism of reducing blood pressure may also be through regulating gene expression of related target proteins,regulating vascular tissue remodeling and extracellular matrix metabolism,reducing inflammatory responses,participating in neuroactive ligand-receptor interactions,calcium signaling pathways,and vascular smooth muscle.