基于网络药理学与动物实验探讨参苓白术散缓解顺铂肾毒性的作用机制  

Mechanism of Shenling Baizhu Powder in Alleviating Cisplatin-Induced Nephrotoxicity Based on Network Pharmacology and Animal Experiments

作　　者：焦琳 殷春霞 夏琦 曹丽芬 余万霖 邓时贵 JIAO Lin;YIN Chunxia;XIA Qi;CAO Lifen;YU Wanlin;DENG Shigui(The Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou Guangdong China 510006;The Second Clinical College of Guangzhou University of Chinese Medicine,Guangzhou Guangdong China 510006)

机构地区：[1]广州中医药大学第二附属医院,广东广州510006 [2]广州中医药大学第二临床医学院,广东广州510006

出　　处：《中医学报》2023年第6期1273-1284,共12页Acta Chinese Medicine

基　　金：国家自然科学基金项目(82104728);广东省中医药管理局基金项目(20212084)。

摘　　要：目的:基于网络药理学、分子对接和动物实验对参苓白术散缓解顺铂所致肾毒性(cisplatin nephrotoxicity,C-IN)的核心活性成分及潜在作用机制进行探讨。方法:运用中药系统药理学数据库与分析平台等数据库及文献检索初步获取参苓白术散组方中药的活性成分并预测其靶点;利用在线人类孟德尔遗传数据库、人类基因数据库、Drugbank数据库获取C-IN的靶点;取参苓白术散活性成分靶点与C-IN疾病相关靶点录入Venny 2.1.0软件,绘制韦恩图,得到两者的交集靶点。利用STRING数据库构建交集靶点的蛋白质相互作用(protein-protein interaction,PPI)网络并进行拓扑分析筛选核心靶点;运用DAVID数据分析平台进行基因本体(gene ontology,GO)富集分析及京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析;选取关键靶点及核心活性成分,使用AutoDock软件进行分子对接。SPF级雄性C57BL/6J小鼠24只随机分为对照组、模型组、减毒组及参苓白术散组,每组6只,模型组和减毒组小鼠每3天腹腔注射1次顺铂注射液(3 mg·kg^(-1))诱导肾损伤,减毒组同时灌胃给予参苓白术散治疗(3 g·kg^(-1)),参苓白术散组仅灌胃给予参苓白术散(3 g·kg^(-1)),对照组每天给予等量的生理盐水。30天后处死小鼠,采用电感耦合等离子体质谱检测肾组织内铂离子含量;脲酶法测定血清尿素氮(blood urea nitrogen,BUN)水平;肌氨酸氧化酶法测定血清肌酐(creatinine,Cre)的水平;HE染色观察肾组织病理变化;PCR检测肾组织AKT1 mRNA、TP53 mRNA、PIK3R1 mRNA、MAPK1 mRNA、MAPK3 mRNA水平。结果:参苓白术散组方中药活性成分204个,相关靶点335个;C-IN疾病相关靶点1 298个,交集靶点137个。利用Cytoscape 3.8.2软件分析参苓白术散“有效成分-交集靶点”网络得到排名前3位的核心活性成分为槲皮素、山柰酚、木犀草素。PPI网络分析筛选出核心靶点分别�Objective:Based on network pharmacology,molecular docking technology,and animal experiments,to explore the core active ingredients and potential mechanism of Shenling Baizhu Powder in alleviating cisplatin-induced nephrotoxicity(C-IN).Method:The active components of Shenling Baizhu Powder were preliminarily obtained and their targets were predicted through databases such as the Traditional Chinese Medicine System Pharmacology Database(TCMSP)and literature retrieval.Utilizing the Online Mendelian Inheritance in Man(OMIM),the human gene database(GeneCards),and the Drugbank database to obtain the targets of C-IN.The active component targets of Shenling Baizhu Powder and C-IN disease-related targets were input into Venny 2.1.0 software,and a Venn diagram was drawn to obtain the intersection targets of the two.The STRING database was used to build a PPI network of intersection targets and perform topology analysis to screen core targets.The DAVID data analysis platform was to conduct gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis.Finally,select key targets and core active ingredients,and use AutoDock software for molecular docking.24 male C57BL/6J mice of SPF grade were randomly divided into control group,model group,attenuated group,and Shenling Baizhu Powder group,with 6 mice in each group.The mice in the model group and the attenuated group were intraperitoneally injected with cisplatin injection(3 mg·kg-1)for every 3 days to induce renal injury,and the mice in the attenuated group were given Shenling Baizhu Powder(3 g·kg-1)by intragastric administration at the same time.The Shenling Baizhu Powder was only given Shenling Baizhu Powder(3 g·kg-1)by intragastric administration,and the control group was given the same amount of normal saline every day.The mice were sacrificed 30 days later,and the content of platinum ions in kidney tissue was detected by inductively coupled plasma mass spectrometry(ICP-MS).The level of serum urea nitrogen(B

关 键 词：参苓白术散 顺铂肾毒性 网络药理学 分子对接 动物实验 小鼠 

分 类 号：R285[医药卫生—中药学]