基于水负荷动物模型及生物信息学虎杖利湿作用的初步研究  

Preliminary study on the dehumidification effect of Huzhang(Polygoni Cuspidati Rhizoma et Radix)based on waterloaded model in mice and bioinformatics

作　　者：江莉媛 李杨松 张瑾 罗婕 张桂荣 朱宝洁 龙飞[1] 郭力[1] JIANG Liyuan;LI Yangsong;ZHANG Jin;LUO Jie;ZHANG Guirong;ZHU Baojie;LONG Fei;GUO Li(School of Pharmacy,State Key Laboratory of Southwest Characteristic Chinese Medicine Resources,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,Sichuan)

机构地区：[1]成都中医药大学药学院,西南特色中药资源国家重点实验室,四川成都611137

出　　处：《中药与临床》2024年第3期36-45,共10页Pharmacy and Clinics of Chinese Materia Medica

基　　金：达州市科技计划项目(21DWHZ0002)。

摘　　要：目的:通过制备小鼠水负荷模型观察虎杖的利湿作用,并基于生物信息学初步探讨其发挥作用的物质基础及可能机制。方法:设置虎杖水提液不同剂量组(9.2、4.6、2.3 g·kg^(-1))构建小鼠水负荷模型;采用ICP-OES法测定小鼠尿液中的钠钾离子浓度;在TCMSP数据库预测虎杖活性成分靶点,Genecards数据库获取湿病相关靶标;取两者交集构建PPI网络并优化,利用Cytoscape3.8.0软件构建“药物-成分-靶点-疾病-通路”网络;在DAVID6.8数据库富集分析交集靶点;借助AutoDock Tools-1.5.7软件进行分子对接。结果:实验表明虎杖水提液中剂量组(4.6 g·kg^(-1))利尿效果显著(P<0.05),可促进钠、钾离子排泄。网络数据库及软件高通量分支和整体筛选中获取虎杖活性成分27个,药物和湿病交集靶点275个;核心靶点为STAT3、TP53、SRC;活性成分包括芹菜素、木犀草素、槲皮素等;相关通路主要涉及AGE-RAGE信号通路、催乳素信号通路、HIF-1信号通路。结论:通过网络可视图及网络组学分析技术初步预测了虎杖发挥利湿作用的关键成分、靶点及相关通路,可为其利湿功效的物质基础研究和临床应用提供理论依据。Objective:The dehumidification effect of Huzhang was observed by preparing a water-loaded model in mice and the material basis and possible mechanism of its effect were discussed based on bioinformatics.Methods:In animal experiments,the water-loaded model of mice was constructed in different dose groups(9.2,4.6,2.3 g·kg^(-1))of Huzhang.The urinary sodium and potassium ion concentration was determined by ICP-OES method.The TCMSP database was used to predict Huzhang active ingredient targets,and the Genecards database was used to obtain dampness-related targets.The PPI network diagram was constructed and optimized by intersection of the two databases results and a"drug-component-target-disease-pathway"network using Cytoscape 3.8.0 software was constructed.Intersection targets were enriched and analyzed in DAVID6.8 database.Molecular docking was carried out with AutoDock Tools-1.5.7 software.Results:Animal experiments showed that the diuretic effect was significant in the dose group of medium-dose group(4.6 g·kg^(-1))of Huzhang aqueous extraction(P<0.05),which could promote the excretion of sodium and potassium ions.The network database and software obtained 27 active ingredients of Huzhang and 275 intersection targets of drug and dampness disease.The core targets were STAT3,TP53,and SRC.The active ingredients include apigenin,luteolin,and quercetin etc.Related pathways mainly included AGE-RAGE signaling pathway,Prolactin signaling pathway,HIF-1 signaling pathway.Conclusion:The key components,targets and related pathways of Huzhang are predicted by network visualization and network omics analysis techniques,which can provide theoretical basis for material basic research and clinical application of Huzhang.

关 键 词：虎杖 水负荷模型 生物信息学 利湿 利尿作用 

分 类 号：R285.5[医药卫生—中药学]