贺潇 蒋伟平 刘起立 黄丽玲 毛璟弢 蔡蔚

〔摘要〕 目的 利用网络药理学和分子对接技术预测芪金合剂（黄芪、金钱草）治疗肾结石的作用机制及潜在靶点。方法 利用多个数据库获取药物有效成分、疾病靶点，取两者交集基因;使用Cytoscape 3.8.0软件构建“中药-成分-靶点”调控网络，将交集靶基因导入STRING数据库，构建蛋白质相互作用网络;并对交集基因进行拓扑分析、GO和KEGG富集分析;将有效成分与核心基因分子对接，计算最低结合能，制作分子对接模型图。结果 获得黄芪有效成分21种，金钱草有效成分10种，黄芪作用靶点396个，金钱草作用靶点263个，交集基因109个;根据KEGG富集分析结果获得作用通路9条;“中药-成分-靶点”网络图中芪金合剂的有效成分为槲皮素、山柰酚、异鼠李素;槲皮素与核心基因分子对接结合稳定。结论 芪金合剂可通过多靶点、多通路、多成分治疗肾结石，槲皮素、山柰酚、异鼠李素可能是其治疗作用的主要有效成分，其潜在的作用机制与炎症、氧化应激反应、代謝、激素及免疫等通路密切相关，其作用靶点可能与AKT1、MAPK1、MAPK14、TNF、ESR1、JUN、FOS、TP53、MYC等多个基因有关。

〔关键词〕 芪金合剂;肾结石;网络药理学;分子对接;作用机制

〔中图分类号〕R285.5       〔文献标志码〕A        〔文章编号〕doi：10.3969/j.issn.1674-070X.2021.12.015

Mechanism of Qijin Mixture in the Treatment of Kidney Stones Based on Network

Pharmacology and Molecular Docking

HE Xiao1， JIANG Weiping1， LIU Qili1， HUANG Liling1， MAO Jingtao1， CAI Wei2*

（1. Hunan University of Chinese Medicine， Changsha， Hunan 410208， China; 2. The First Affiliated Hospital of

Hunan University of Chinese Medicine， Changsha， Hunan 410007， China）

〔Abstract〕 Objective The mechanism and potential targets of Qijin Mixture [Huangqi （Astragali Radix）， Jinqiancao （Lysimachiae Herba）] in the treatment of kidney stones were predicted by network pharmacology and molecular docking technology. Methods Multiple databases were used to obtain drug active ingredients and disease targets， their intersection genes were selected; Cytoscape 3.8.0 software was used to construct a “traditional Chinese medicine-component-target” regulatory network， and the intersection target genes were imported into the STRING database to construct a protein-protein interaction network; and topological analysis， GO and KEGG enrichment analysis were performed for the intersection genes; the active ingredients and the core gene molecules were docked， the lowest binding energy was calculated， and a molecular docking model diagram was made. Results 21 kinds of active ingredients of Huangqi （Astragali Radix） were obtained， 10 kinds of active ingredients of Jinqiancao （Lysimachiae Herba） were obtained， 396 targets of Huangqi （Astragali Radix） were obtained， 263 targets of Jinqiancao （Lysimachiae Herba） were obtained， and 109 intersection genes were obtained. According to the results of KEGG enrichment analysis， 9 action pathways were obtained; the effective ingredients of Qijin Mixture in the network diagram of “traditional Chinese medicine-component-target” were quercetin， kaempferol and isorhamnetin; quercetin was stable in docking and binding with core gene molecules. Conclusion Qijin Mixture can treat kidney stones through multiple targets， multiple pathways， and multiple components. Quercetin， kaempferol and isorhamnetin may be the main active components of its therapeutic effect， and its potential mechanism of action is closely related to inflammation， oxidative stress response， metabolism， hormone and immune pathways， and its targets may be related to multiple genes such as AKT1， MAPK1， MAPK14， TNF， ESR1， JUN， FOS， TP53， MYC.

〔Keywords〕 Qijin Mixture; kidney stones; network pharmacology; molecular docking; mechanism

肾结石是泌尿外科常见的疾病之一，其发病率已达到1%～20%，呈逐年上升趋势，治疗后其复发率超过50%[1]，且复发结石患者再发的可能性更大[2]。现其手术治疗多以微创为主，包括体外冲击波碎石术、经皮肾镜取石术、输尿管软镜取石术等。随着腔镜微创技术的不断成熟，肾结石的治疗手段也在不断增多，但如何减少术后残石、结石复发率高的现状依然是众多学者研究的热点。……