仙芪消渴饮治疗糖尿病肾脏病的潜在作用机制  

Mechanism of Xianqixiaoke Decoction in the Treatment of Diabetic Kidney Disease

作　　者：刘梦阳[1] 李海勇 郭燕 张富赓[4] 刘征堂[1] LIU Mengyang;LI Haiyong;GUO Yan;ZHANG Fugeng;LIU Zhengtang(Department of Geriatrics,Xiyuan Hospital of China Academy of Chinese Medical Sciences,Beijing 100091,China;Department of Rehabilitation,Suzhou Integrated Traditional Chinese and Western Medicine Hospital,Suzhou 215101,China;Department of T.C.M,Xiangshan Community Health Service Center,Beijing 100093,China;Department of Pharmacy,Tianjin Huanhu Hospital,Tianjin 300350,China)

机构地区：[1]中国中医科学院西苑医院老年病科,北京100091 [2]苏州市中西医结合医院康复科,苏州215101 [3]北京香山社区卫生服务中心中医科,北京100093 [4]天津市环湖医院药剂科,天津300350

出　　处：《西南医科大学学报》2022年第6期493-500,共8页Journal of Southwest Medical University

基　　金：科技部国家重点研发计划(2020YFC2006103);第四批全国中医优秀人才(临床、基础)研修项目(国中医药人教发[2017]24号)。

摘　　要：目的基于网络药理学和分子对接法研究仙芪消渴饮治疗糖尿病肾脏病的潜在作用机制,为经典名方再开发提供循证医学支撑。方法在检索数据库和查阅文献后对仙芪消渴饮的活性成分和相应靶点作出预测;从GEO数据库中获取糖尿病肾脏病相关基因芯片数据并分析筛选出差异基因序列确定为DKD靶点;通过Cytoscape软件及Bisogenet、CytoNCA、MCODE插件功能实现网络构建、拓扑分析与模块化分析;在R3.6.2环境下运行生物信息软件包Bioconductor实现富集分析;完成分子对接以验证活性成分与关键靶点的亲和力。结果仙芪消渴饮共涉及193个活性成分、24个关键靶点;围绕从蛋白互作核心网络中提取的2个模块,GO分析共得到588个生物学过程、47个细胞组分、72个分子功能;KEGG分析共富集30条通路,经拣择发现与糖尿病肾脏病关系较为密切的信号通路与生物学过程主要包括PI3K-Akt信号通路、甲状腺激素信号通路、泛素-蛋白酶体系统和内质网应激。经分子对接验证,槲皮素、熊竹素、食脂素、木犀草素可与其蛋白靶标有效结合,这四种可能活性成分作为药效分子具有一定肾脏保护作用。结论仙芪消渴饮是通过多成分、多靶点、多通路对糖尿病肾脏病进行干预而发挥作用。Objective This study was designed to explore the mechanism of Xianqixiaoke Decoction in the treatment of diabetic kidney disease(DKD)by network pharmacology and molecular docking,aiming to provide basis for redevelopment of ancient classical famous formulas.Methods The active ingredients and targets of Xianqixiaoke Decoction were obtained by consulting references and docament retrieval.Genetic chips related to DKD were screened through GEO database and differentially expressed genes(DEGs)were acquired by differential analysis,which were taken as targets associated with DKD.The network maps of drug-components-targets-disease were constructed by Cytoscape software after intersecting the two target data sets.The essential functional modules of PPI core network which was searched by network topology were built by MCODE.The related GO gene function and KEGG pathway enrichment analyses were carried out by applying Bioconductor software.The molecular docking was completed to verify the affinities of active components and key targets.Results A total of 193 active ingredients and 24 targets were obtained.A total of 588 biological processes,47 cell components and 72 molecular functions were obtained by GO analysis from the two modules extracted from the protein interaction core network.A total of 30 pathways were enriched by KEGG analysis.The signal pathways and biological processes closely related to diabetic kidney disease mainly included PI3K-Akt signaling pathway,thyroid hormone signaling pathway,ubiquitin-proteasome system and endoplasmic reticulum stress.Four active ingredients verified by molecular docking,including quercetin,jaranol,DFV and luteolin,played a part in kidney protection.Conclusion Xianqixiaoke decoction played a role in the treatment of diabetic kidney disease through the intervention of multiple components,multiple targets and multiple pathways.

关 键 词：网络药理学 分子对接 仙芪消渴饮 糖尿病肾脏病 关键靶点 

分 类 号：R285.5[医药卫生—中药学]