藏药十五味赛尔斗丸治疗豚鼠胆囊炎的作用机制研究  

Action Mechanism of Tibetan Medicine Shiwuwei Saierdou Pill in Treatment of Guinea Pig Cholecystitis

作　　者：陈蔚 马腾飞 武慧超[1,2] 刘媛媛 仁青东主[3] 张金魁 任小巧[1,2] CHEN Wei;MA Tengfei;WU Huichao;LIU Yuanyuan;RENQING Dongzhu;ZHANG Jinkui;REN Xiaoqiao(Beijing University of Chinese Medicine,Beijing China 100029;Institute of Ethnic Medicine,Beijing University of Chinese Medicine,Beijing China 100029;Qinghai University,Xining Qinghai China 810016;Qinghai Institute of Tibetan Medicine,Xining Qinghai China 810016)

机构地区：[1]北京中医药大学,北京100029 [2]北京中医药大学民族医药学研究所,北京100029 [3]青海大学,青海西宁810016 [4]青海藏医药研究院,青海西宁810016

出　　处：《中医学报》2022年第8期1676-1687,共12页Acta Chinese Medicine

基　　金：青海省重点研发与转化专项项目(2020-SF-C33)。

摘　　要：目的:运用网络药理学及分子对接技术探讨藏药十五味赛尔斗丸治疗胆囊炎的作用机制,并以胆囊炎豚鼠模型验证其核心靶点和通路。方法:通过检索PubMed、CNKI、万方、维普等文献数据库,结合中药系统药理学数据库与分析平台和中药分子机制的生物信息学分析工具搜集十五味赛尔斗丸各药的化学成分。通过Swiss Target Prediction数据库筛选活性成分相关靶点。在人类基因数据库、在线人类孟德尔遗传数据库中检索胆囊炎相关靶点。将有效成分相关靶点与胆囊炎靶点进行映射,绘制venny图,交集靶点即为十五味赛尔斗丸治疗胆囊炎的潜在靶点,运用Cytoscape3.8.2软件构建“药物-活性成分-潜在靶点-疾病”网络图并进行网络拓扑分析筛选关键成分。将潜在靶点输入STRING数据库得出蛋白质相互作用关系,导入Cytoscape3.8.2软件中获得PPI网络,通过网络拓扑分析获得核心靶点。将潜在靶点导入DAVID数据库进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。采用Schr9dinger Maestro软件中的Glide模块对关键成分及靶点进行分子对接。随机从60只雌雄各半清洁级豚鼠中选12只为正常组,其余48只豚鼠复制胆囊炎模型。将造模成功的48只豚鼠随机分为模型组、十五味赛尔斗丸水溶液组(0.35 g·kg^(-1))、十五味赛尔斗丸醇提组(0.12 g·kg^(-1))、消炎利胆片组(0.36 g·kg^(-1)),每组12只,各给药组给予相应剂量的药物进行灌胃,正常组和模型组给予等体积的生理盐水,每天1次,连续15 d。HE染色观察胆囊组织病理损伤;ELISA法测定血清和胆汁中TNF-α的含量;实时荧光定量PCR检测胆囊中NF-κB、TNF-α的mRNA表达水平;Western Blot检测胆囊组织中NF-κB蛋白表达水平。结果:共获得活性成分193个及相关靶点1 069个,胆囊炎相关靶点702个,潜在靶点141个�Objective:To explore the mechanism of action of Tibetan medicine Shiwuwei Saierdou Pill in the treatment of cholecystitis using network pharmacology and molecular docking technology,and to verify its core targets and pathways with a guinea pig model of cholecystitis.Methods:The chemical constituents of Shiwuwei Saierdou Pills were collected by searching literature databases such as PubMed,CNKI,Wanfang,VIP,etc.,combined with the TCM system pharmacology database and analysis platform and the bioinformatics analysis tool of TCM molecular mechanism.Active ingredient-related targets were screened through the Swiss Target Prediction database.Cholecystitis-related targets were searched in the Human Genome Database,the online Human Mendelian Inheritance Database.The active ingredient-related targets and cholecystitis targets were mapped,the Venny diagram was drawn,and the intersection targets were potential targets for the treatment of cholecystitis by Shiwuwei Saierdou Pills.Cytoscape 3.8.2 software was used to construct a "drug-active ingredient-potential target-disease" network diagram,and network topology analysis was performed to screen the key components of Shiwuwei Saierdou Pill in the treatment of cholecystitis.Input the potential targets into the STRING database to obtain the protein interaction network relationship,import them into Cytoscape 3.8.2 software to obtain the PPI network,and obtain the core targets through network topology analysis.The potential targets were imported into the DAVID database for gene ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis.Molecular docking of key components and targets was performed using the Glide module in the Schr?dinger Maestro software.12 guinea pigs were randomly selected from 60 male and female half-half clean-grade guinea pigs as the normal group,and the remaining 48 guinea pigs were used to replicate the guinea pig cholecystitis model.The 48 guinea pigs that were successfully modeled were rando

关 键 词：胆囊炎 十五味赛尔斗丸 网络药理学 分子对接 NF-ΚB信号通路 豚鼠 藏药 

分 类 号：R284.2[医药卫生—中药学]