基于网络药理学的泽泻治疗高脂血症不同配伍规律及药效作用机制研究

Study on Different Compatibility Rules and Pharmacodynamic Mechanisms of Alismatis Rhizoma in the Treatment of Hyperlipidemia Based on Network Pharmacology

目的:本文基于网络药理学方法探究泽泻治疗高脂血症不同配伍规律及其内在的药效作用机制。方法:利用中国知网等平台收集泽泻治疗高脂血症的复方,并通过中医传承计算机平台V3.0分析数据,最终筛选出治疗高脂血症配方中与泽泻高频配伍的中药材。使用TCMSP、SymMap、SwissTargetPrediction数据库检索泽泻及其高配伍药材的作用靶点。使用GeneCards、Disgenet、OMIM数据库获取高脂血症的疾病靶点。采用Venny 2.1.0获取药物–疾病交集靶点,使用网站STRING和软件Cytoscape3.9.1进行分析,绘制泽泻及其配伍药材–高脂血症的PPI网络图,以识别核心靶标。利用网站Metascape对共有靶点进行GO和KEGG富集分析,并利用插件Cluego分析泽泻配伍治疗高脂血症核心通路。结果:在泽泻治疗高脂血症的配方中选取了14个与泽泻高频配伍的中药材,其分别为丹参、山楂、茯苓、白术、陈皮、决明子、黄芪、川芎、半夏、荷叶、党参、柴胡、何首乌、甘草。尽管这些不同配伍药材在成分上存在较大差异,但与泽泻配伍后和高脂血症的交集靶点及KEGG信号通路高度重叠。靶点RXRA、NCOA1、IL6、IL1B、TNF、PPARG在各个配伍药材中高频出现且degree值较高,推测其是增强泽泻治疗高脂血症疗效的核心靶点。KEGG通路涉及AGE-RAGE信号通路与糖尿病并发症、胰岛素抵抗、血脂与动脉粥样硬化、癌症、流体剪切应力与动脉粥样硬化。结论:本研究通过网络药理学探究泽泻治疗高脂血症的潜在机理及不同配伍关系对泽泻治疗高脂血症的影响,为高脂血症治疗和基础研究提供新思路。

Objective: This article is based on network pharmacology to explore the different compatibility patterns and internal pharmacological mechanisms of Alismatis Rhizoma in the treatment of hyperlipidemia. Methods: This study collected formulas containing Alismatis Rhizoma in treating Hyperlipidemia on the CNKI. It analyzed data using the traditional Chinese medicine inheritance computing platform V3.0 and selected Chinese medicinal herbs with higher compatibility with Alismatis Rhizoma in the formulas for treating Hyperlipidemia. This paper retrieved the action targets of Alismatis Rhizoma and its highly compatible medicinal herbs using TCMSP, SymMap, and SwissTargetPrediction databases;obtained disease targets of hyperlipidemia using GeneCards, Disgenet, and OMIM databases;used Venny 2.1.0 to acquire the intersection targets of drugs-diseases;performed analysis using the STRING website and Cytoscape 3.9.1 software to draw the PPI network diagram of Alismatis Rhizoma and its compatible medicinal herbs with hyperlipidemia to identify core targets;conducted GO and KEGG enrichment analysis of shared targets using the Metascape website;and analyzed core pathways for treating hyperlipidemia with Alismatis Rhizoma using the Cluego plugin. Results: 14 Chinese medicinal herbs with high-frequency compatibility with Alismatis Rhizoma were selected in the formula for treating Hyperlipidemia, including Danshen, Hawthorn, Fuling, Baizhu, Chenpi, Juemingzi, Huangqi, Chuanxiong, Banxia, Heye, Dangshen, Chaihu, Heshouwu, and Gancao. Although there are significant differences in composition among different compatibility medicinal herbs, their intersection targets and KEGG signalling pathways with Alismatis Rhizoma and Hyperlipidemia after compatibility are highly overlapping. The targets RXRA, NCOA1, IL6, IL1B, TNF, and PPARG are frequently present in various compatible medicinal herbs and rank high in degree values. Presumably, it is the core target for enhancing the efficacy of Alismatis Rhizoma in treating Hyperlipidemia through compatibility. The KEGG pathway involves the AGE-RAGE signaling pathway in diabetes complications, insulin resistance, lipids and atherosclerosis, pathways in cancer, fluid shear stress and atherosclerosis. Conclusion: This study explores the potential mechanism of Alismatis Rhizoma in treating Hyperlipidemia through network pharmacology and the impact of different compatibility relationships on Alismatis Rhizoma in treating Hyperlipidemia, providing new ideas for the treatment and basic research of Hyperlipidemia.