基于网络药理学探究四神煎治疗糖尿病周围神经病变的分子机制  

Exploration on Molecular Mechanism of Sishenjian in Treating Diabetic Peripheral Neuropathy Based on Network Pharmacology

作　　者：黄伟东 廖佳 郑玲玲 袁腾骅 吴栓 

机构地区：[1]广州中医药大学,广东佛山528200 [2]广州中医药大学针灸康复临床医学院,广东广州510006 [3]暨南大学研究生院,广东广州510632 [4]广东省中西医结合医院,广东佛山528200 [5]广东省中西医结合医院脊柱骨科,广东佛山528200

出　　处：《大众科技》2023年第1期92-97,共6页Popular Science & Technology

基　　金：广东省中医药局科研项目“基于数据挖掘技术探究‘三脏一体’辨证模式治疗KOA的组方规律及核心处方研究”(20202036)。

摘　　要：目的:基于网络药理学及分子对接技术,探究四神煎治疗糖尿病周围神经病变(Diabetic peripheral neuropathy,DNP)的药理分子机制,为经典方剂临床应用提供初步的现代理论依据。方法:通过Batman-TCM数据库(http://bionet.ncpsb.org/batman-tcm/)获取黄芪、石斛、牛膝、远志、金银花五味中药的主要化学成分及靶点信息;利用String11.0数据库(https://www.string-db.org/)进行蛋白质相互作用分析,构建PPI网络并进行可视化分析,预测其中发挥作用的主要蛋白靶点。在Metascape数据库进一步分析核心靶点参与的生物过程及通路,采用CytoScape 3.8.0软件构建“四神煎成分-核心靶点-通路”关系网,分析其中主要发挥作用的成分及关键靶标,最后运用AutoDockTools-1.5.6进行分子对接,对接结果用PyMOL显示。结果:得到四神煎治疗DNP的活性成分79个,对应靶点456个,交集核心靶点113个,预测四神煎治疗DNP的主要活性成分为茉莉酮,核心基因ALB、TNF、PTGS2、CREB1、CAT、PPARG、NOS3、ESR1、PTGS1、AR等。分子对接中活性成分与目标蛋白的结合能均低于-1.0 kcal/mol,大部分靶点与成分的结合活性较好。生物富集分析中,大部分通路与DNP密切相关,其中胃酸分泌通路、Apelin信号通路、对氧化应激的反应、抗氧化、氧结合等富集通路为四神煎调治DNP的关键代谢通路。结论:研究发现四神煎能通过多成分、多靶点、多通路治疗DNP患者,主要活性成分与目标蛋白的对接结果较好,为四神煎治疗DNP进一步提供现代药理分子机制,为临床上运用四神煎治疗DNP提供初步的理论基础。Objective: Based on network pharmacology and molecular docking technology, to explore the pharmacological mechanism and molecular of Sishenjian in treating diabetic peripheral neuropathy(DPN), and to provide preliminary modern theoretical basis for the clinical application of classical prescriptions. Methods: Through Batman-TCM database(http://bionet.ncpsb.org/batman-tcm/)to obtain the main chemical components and target information of five traditional Chinese medicines: Astragalus, Dendrobium,Achyranthes bidentata, Polygala tenuifolia and honeysuckle;the protein interaction was analyzed by String 11.0 database(https://www.string-db.org/). PPI network was constructed and visual analysis was carried out to predict the main protein targets at play.The biological processes and pathways involved by the core targets were further analyzed in the Metascape database, and the relationship network of "Sishenjin components-core targets-pathways" was constructed by CytoScape 3.8.0 software, and the main components and key targets were analyzed. Finally, AutoDockTools-1.5.6 was used for molecular docking, and the docking results were displayed by Pymol.Results: 79 active components of Sishenjian in the treatment of DNP, 456 corresponding targets and 113core targets were obtained. It was predicted that the main active components of Sishenjian in the treatment of DNP were jasmonone and the core genes ALB, TNF, PTGS2,CREB1, CAT PPARG, NOS3, ESR1, PTGS1, AR and so on. In molecular docking, the binding energy of active components and the target proteins were all lower than-1.0 kcal/mol, and most of the targets had good binding activity with the components. In bioaccumulation analysis, most of the pathways were closely related to DNP, among which gastric acid secretion pathway, Apelin signal pathway, reaction to oxidative stress, antioxidant, oxygen binding and other enrichment pathways were the key metabolic pathways of Sishenjian in the treatment of DNP. Conclusion: This study found that Sishenjian could treat patients with DNP t

关 键 词：四神煎 糖尿病周围神经病变 网络药理学 分子对接 靶点预测 

分 类 号：R587[医药卫生—内分泌]