| 杨伟林,吴玲云,李文进,等.基于网络药理学和分子对接探究木防己汤对慢性心力衰竭的治疗机制[J].浙江中医药大学学报,2023,47(6):669-677, 695. |
| 基于网络药理学和分子对接探究木防己汤对慢性心力衰竭的治疗机制 |
| Mechanism of Mufangji Decoction for the Treatment of Chronic Heart Failure by Network Pharmacology and Molecular Docking |
| DOI：10.16466/j.issn1005-5509.2023.06.017 |
| 中文关键词: 木防己汤 慢性心力衰竭 网络药理学 分子对接 HSP90AA1 PTGS2 治疗机制 |
| 英文关键词: Mufangji Decoction chronic heart failure network pharmacology molecular docking HSP90AA1 PTGS2 therapeutic mechanism |
| 基金项目:湖州市科学技术局研究项目(2020GY89) |
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| 中文摘要: |
| [目的] 通过网络药理学及分子对接分析木防己汤治疗慢性心力衰竭(chronic heart failure，CHF)的具体机制并进行验证。[方法] 使用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform，TCMSP)获取木防己汤的主要有效成分及治疗靶点，同时使用人类基因数据库(Human Gene Database，GeneCards)数据库、药物靶标数据库(Therapeutic Target Database，TTD)、人类孟德尔遗传在线(Online Mendelian Inheritance in Man，OMIM)数据库、药品数据与药物靶点(DrugBank)、遗传药理学与药物基因组学数据库(Pharmacogenetics and Pharmacogenomics Knowledge Base，PharmGkb)等数据库获取CHF的相关基因，并通过Cytoscape 3.9软件构建木防己汤-靶点-CHF网络；对获取的治疗靶点分别进行蛋白互作(protein-protein interaction，PPI)分析、基因本体(gene ontology，GO)富集分析及京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)信号通路富集分析，最后使用AutoDockVina、PyMol软件对木防己汤治疗CHF主要成分及核心靶点进行分子对接验证。[结果] 共获取木防己汤主要有效成分32个，治疗靶点326个，CHF相关基因10 693个，木防己汤治疗CHF靶点104个。KEGG分析显示脂质与动脉粥样硬化、肿瘤受体激活、神经活性配体与受体相互作用、阿尔茨海默病、钙信号通路排名靠前。拓扑分析结果显示木防己汤治疗CHF核心靶点为热休克蛋白90α家族A类成员1(heat shock protein 90 ɑ family class A member 1，HSP90AA1)、前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2，PTGS2)。分子对接结果显示木防己汤治疗CHF关键靶点与主要活性成分对接良好。[结论] 木防己汤治疗CHF具有多靶点、多通路的特点，其治疗机制涉及HSP90AA1、PTGS2等蛋白，本研究为CHF相关生物实验研究及新药开发提供了临床支持及理论参考。 |
| 英文摘要: |
| [Objective] To analyze and validate the specific mechanism of Mufangji Decoction for the treatment of chronic heart failure(CHF) through network pharmacology and molecular docking. [Methods] The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) was used to obtain the main active ingredients and therapeutic targets of Mufangji Decoction， while Human Gene Database(GeneCards)， Therapeutic Target Database(TTD)， Online Mendelian Inheritance in Man(OMIM)， DrugBank， Pharmacogenetics and Pharmacogenomics Knowledge Base(PharmGkb) and other databases were used to obtain the genes related to CHF， finally Cytoscape 3.9 software was used to construct the Mufangji Decoction-target-CHF network and the main active ingredients of Mufangji Decoction for the treatment of CHF were got; protein-protein interaction(PPI) analysis， gene ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway enrichment analysis were performed on the targets of Mufangji Decoction for the treatment of CHF， and finally molecular docking verification of the main components and core targets of Mufangji Decoction for the treatment of CHF was performed by using AutoDockVina and PyMol software. [Results] Thirty-two main active ingredients and 326 therapeutic targets were obtained from Mufangji Decoction，10 693 CHF-related genes and 104 CHF targets treated with Mufangji Decoction were obtained. Lipid and atherosclerosis， tumor receptor activation， neuroactive ligand-receptor interaction， Alzheimer’s disease and calcium signaling pathways ranked highly according to KEGG analysis. Topological analysis showed that heat shock protein 90 ɑ family class A member 1(HSP90AA1) and prostaglandin-endoperoxide synthase 2(PTGS2) were the core targets of Mufangji Decoction for the treatment of CHF. Molecular docking results showed that the key targets of Mufangji Decoction for the treatment of CHF dovetailed well with the main active ingredients. [Conclusion] Mufangji Decoction has multi-target and multi-pathway characteristics for the treatment of CHF， and its therapeutic mechanism involves HSP90AA1 and PTGS2. The results also provide clinical support and theoretical reference for CHF-related biological experimental research and new drug development. |
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