2024年3月15日发(作者：)

护理研究 2023 年 8 月第 37 卷第 16 期（总第 732 期）

·2853·

· 科研论著 ·

基于网络药理学和分子对接技术探讨沙棘

活性成分对非酒精性脂肪肝作用机制

高健

1

，吴胜男

1

，王晓静

2

，纪景馨

2

，张然

2

，程景民

1*

1.山西医科大学管理学院，山西 030001；2.山西医科大学公共卫生学院

Abstract Objective：To analyze and study the molecular mechanism of active ingredients of sea buckthorn on non-alcoholic fatty liver

disease（NAFLD） through network pharmacology and molecular docking s：The high⁃throughput sequencing data of

NAFLD was retrieved from the GEO database，and the differential expression analysis of the R language edgeR package was used to

obtain the intersection of the differential genes and the corresponding targets of key components of sea buckthorn retrieved from the

TCMSP database to obtain potential targets of sea buckthorn to interfere with set enrichment analysis was used to study

potential target⁃related cellular functions and signaling pathways，and Cytoscape was used to construct a component⁃target⁃pathway

interaction uently，protein interaction network analysis（PPI） and network topology analysis（Degree） were performed to

determine the core intervention targets，and the virtual docking of core targets and core components was performed through AutoDock

Vina and PyMOL open source tools to predict the relationship between ligands and lar mechanism of s：

The component⁃target⁃pathway network was constructed by 159 nodes and 387 pairs of lar docking results showed

that 10 active substances，including quercetin，flavonoids，kaempferol，linolenic acid，isorhamnetin，myricetin，coumarin，ursolic acid，rutin

and stigmasterol，interact with JUN，MMP9，FGF2，VCAM1 ，CDKN1A，ACE，SERPINE1，SPP1，NOS3 and CCNA2，these 10 core

targets have high onal enrichment and pathway enrichment analysis mainly obtained biological processes of fatty acid

synthesis and metabolism.62 active ingredients such as quercetin in sea buckthorn were shown to interfere with the development of

NAFLD by regulating 61 targets such as transcription factor sion：A variety of active components in sea buckthorn may play

a role in preventing or intervening in the development of NAFLD by affecting lipid accumulation，reducing inflammatory response and

scavenging reactive oxygen species through multiple targets and multiple organic acids such as ursolic acid rich in sea

buckthorn have great potential to interfere with NAFLD.

Keywords transcriptomics； seabuckthorn； non⁃alcoholic fatty liver disease，NAFLD； network pharmacology； molecular docking

摘要 目的:通过网络药理学以及分子对接技术对沙棘活性成分干预非酒精性脂肪肝病（non⁃alcoholic fatty liver disease，NAFLD）

的分子作用机制深入分析研究。方法:在GEO数据库检索非酒精性脂肪肝病的高通量测序数据，通过R语言edgeR包差异表达分

析后，将差异基因与TCMSP数据库检索到的沙棘关键成分对应靶点取交集，得到沙棘干预非酒精性脂肪肝病的潜在靶点。利用基

因集富集分析，研究潜在靶点相关细胞功能和信号通路，并使用Cytoscape构建成分⁃靶点⁃通路三者作用网络。随后进行蛋白质互

作网络（PPI）和网络拓扑分析Degree确定核心干预靶点，并通过AutoDock Vina和PyMOL开源工具进行核心靶点与核心成分的虚

拟对接工作，预测配体与受体之间的分子作用机制。结果:成分⁃靶点⁃通路网络由159个节点以及387对互作关系构建而成。分子对

接结果显示，槲皮素、黄酮、山柰酚、亚麻酸、异鼠李素、杨梅黄酮、香豆素、熊果酸、芦丁和豆甾醇共10种活性物质与JUN、MMP9、

FGF2、VCAM1、CDKN1A、ACE、SERPINE1、SPP1、NOS3和CCNA2 10个核心靶点有较高亲和性。功能富集和通路富集分析主

要得到脂肪酸合成与代谢的生物过程。沙棘中槲皮素等62种活性成分显示通过调节转录因子JUN等61个靶点影响干预非酒精性

脂肪肝病的发展。结论:沙棘中多种活性成分可能通过多靶点、多通路影响脂质积累、减弱炎症反应和清除活性氧从而发挥预防或

干预非酒精性脂肪肝病病情发展的作用。沙棘中富含的熊果酸等有机酸干预非酒精性脂肪肝病潜力巨大。

关键词 转录组学；沙棘；非酒精性脂肪肝；网络药理学；分子对接

doi:10.12102/.1009-6493.2023.16.001

GAO　Jian, WU　Shengnan, WANG　Xiaojing, JI　Jingxin, ZHANG　Ran, CHENG　Jingmin

School of Management, Shanxi Medical University, Shanxi 030001 China

Corresponding Author CHENGJingmin,E⁃mail:********************

Study on mechanism of active ingredient in seabuckthorn on non⁃alcoholic fatty liver based on network

pharmacology and molecular docking

非酒精性脂肪肝病（non⁃alcoholic fatty liver disease，

NAFLD）包括脂肪变性、脂肪肝炎（non⁃alcoholic

steatohepatitis，NASH）、肝纤维化，最终导致肝硬化及

肝细胞癌症的广泛性系列疾病

[1]

。据流行病学调查数

据显示，全球成人非酒精性脂肪肝病的患病率高达

23%~25%，其中20%非酒精性脂肪肝病病人受脂肪

肝炎的影响

[2]

。现阶段，在“二次打击”学说不断发展

的基础上，针对除脂肪变性、氧化应激以外的胰岛素抵

抗、线粒体功能紊乱、脂质毒性等多重平行打击在致病

机制方面表明，非酒精性脂肪肝病为多种危险因素的

相互作用导致

[3⁃4]

。考虑到非酒精性脂肪肝病受基因

遗传、表观遗传和环境暴露等诸多复杂因素的相互影

响，除使用非针对性药物治疗或接受身体运动的建议

基金项目 国家自然科学基金青年科学基金项目，编号：71804102；山

西省高校教学改革创新项目，编号：J2021261

作者简介 高健，硕士研究生在读