基于网络药理学方法和分子对接技术探讨刺梨治疗高血脂症的作用机制  

Mechanism of Rosa roxburghii Tratt in treatment of hyperlipidemia based on network pharmacology and molecular docking technology

作　　者：季嘉城 袁敏艳 张硕 唐丽 王鹏娇 张敏 高秀丽 JI Jia-cheng;YUAN Min-yan;ZHANG Shuo;TANG Li;WANG Peng-jiao;ZHANG Min;GAO Xiu-li(State Key Laboratory of Functions and Applications of Medicinal Plants&School of Pharmacy,Guizhou Medical University,Guiyang 550025,China;Experimental Animal Center of Guizhou Medical University,Guiyang 550025,China;Center of Microbiology and Biochemical Pharmaceutical Engineering,Guizhou Medical University,Guiyang 550025,China;Guizhou Provincial Engineering Research Center of Food Nutrition and Health,Guizhou Medical University,Guiyang 550025,China)

机构地区：[1]省部共建药用植物功效与利用国家重点实验室/贵州医科大学药学院 [2]贵州医科大学实验动物中心,贵州贵阳550025 [3]贵州高等学校微生物与生化药学工程中心 [4]贵州省食品营养与健康工程研究中心,贵州贵阳550025

出　　处：《中国药理学通报》2022年第10期1572-1578,共7页Chinese Pharmacological Bulletin

基　　金：贵州省科技计划项目(黔科合支撑[2020]4Y214);贵州省卫生健康委科学技术基金项目(No gzwkj2021-454)。

摘　　要：目的基于实验验证和网络药理学探究刺梨治疗高血脂症的效果和作用机制。方法构建高血脂大鼠模型,通过考察血脂指标和肝脏病理学变化来探究刺梨对高血脂症的治疗作用。采用文献检索法收集刺梨有效成分及靶点;利用GeneCards、OMIM、DrugBank数据库筛选疾病靶点;构建中药-活性成分-潜在靶点网络和蛋白互作(PPI)网络;使用DAVID软件进行靶点GO功能富集分析和KEGG通路富集分析;使用AutoDock进行分子对接。结果刺梨能够明显改善高血脂大鼠的血脂异常和肝脏病理损伤;网络药理学结果显示RXRA、AKT1、ESR1、PIK3R1是刺梨降血脂的关键靶点;分子对接表明Roxburic acid、α-亚麻酸与RXRA、AKT1、ESR1、PIK3R1均有较好的结合性。结论结合药效学实验和网络药理学-分子对接,初步探索了刺梨对高血脂症的治疗作用和可能的作用机制,为深入研究药效物质基础、作用机制以及临床应用提供一定的基础。Aim To explore the ameliorative effects of Rosa roxburghii Tratt on hyperlipidemia and investigate the underlying mechanism by using experimental validation and network pharmacology.Methods The therapeutic effect of Rosa roxburghii Tratt on hyperlipidemia was investigated by constructing a hyperlipidemic rat model and measuring the serum lipid index and liver pathological changes.The literature search method was used to obtain active ingredients and targets of Rosa roxburghii Tratt,the target gene was collected from GeneCards,OMIM,DrugBank database,then generated herbal-active ingredient-potential target networks and protein-protein interactions(PPI)networks.The target GO function enrichment analysis and KEGG pathway enrichment analysis were analyzed by DAVID software.Molecular docking was carried out using AutoDock.Results Rosa roxburghii Tratt could significantly improve dyslipidemia and liver pathological damage in hyperlipidemic rats.Network pharmacology results showed that RXRA,AKT1,ESR1,PIK3R1 were key targets of Rosa roxburghii Tratt to lower blood lipids.Molecular docking showed that Roxburic acid andα-linolenic acid had good binding to RXRA,AKT1,ESR1,and PIK3R1.Conclusions Combined with pharmacodynamic experiments and network pharmacology-molecular docking,the therapeutic effect and possible mechanism of action of Rosa roxburghii Tratt on hyperlipidemia are preliminarily explored,which provides a certain basis for the in-depth study of pharmacodynamic substance basis,mechanism of action and clinical application.

关 键 词：刺梨 高血脂症 动物实验 网络药理学 分子对接 作用机制 

分 类 号：R-332[医药卫生] R282.71R319R589.2