天然产物研究与开发 ›› 2021, Vol. 33 ›› Issue (12): 2119-2135.doi: 10.16333/j.1001-6880.2021.12.017

• 数据研究 • 上一篇    下一篇

基于生物信息学探讨黑果枸杞总黄酮治疗非酒精性脂肪肝的作用机制

阿力米江·奥布力塔力甫,马建宝,伊再提·外力,古丽巴哈尔·卡吾力*   

  1. 新疆医科大学药学院药剂教研室,乌鲁木齐 830011
  • 出版日期:2021-12-28 发布日期:2021-12-30
  • 基金资助:
    新疆天然药物活性组分与释药技术重点实验室项目(XJDX1713)

Study on the mechanism of the total flavonoids from Lycium ruthenicum Murr. in the treatment of non-alcoholic fatty liver disease based on bioinformatics

ALIMIJIANG·Aobulitalifu,MA Jian-bao,YIZAITI·Waili,GULIBAHAER·Kawuli*   

  1. Department of Pharmacology,Xinjiang Medical University,Urumqi 830011,China
  • Online:2021-12-28 Published:2021-12-30

摘要: 本文旨基于生物信息分析揭示非酒精性脂肪肝的关键基因,并基于超高效液相色谱-质谱联用技术(UPLC/MS-MS)、生物信息及分子对接技术识别并探究黑果枸杞总黄酮成分及其治疗非酒精性脂肪肝(NAFLD)的作用机制,为其药效物质基础研究提供参考依据。本研究用GSE89632数据集,其中包括39名NAFLD患者和24名健康对照组。Limma包分析得到3 375个差异基因,再通过WGCNA分析得到19个模块和95个最相关基因。黑枸杞总黄酮通过进行定性分析和靶点预测得到71个活性成分和375个相关基因。疾病基因和成分靶点基因交集得到24个基因,用CytoHubba筛选出10个Hub基因。通过DAVID数据库得到KEGG通路9条,GO分析条目33条。分子对接结果表明,大多数黑果枸杞总黄酮成分与关键靶点具有较好的结合力。生存分析结果中VEGF与HCC的生存分析密切相关。免疫细胞浸润相关性评估分析结果表明,Hub基因与幼稚B细胞、γδT细胞、单核细胞等8种免疫细胞相关。本研究揭示了非酒精性脂肪肝的关键基因、明确了黑果枸杞总黄酮成分、预测了黑枸杞总黄酮成分治疗非酒精性脂肪肝的作用机制并初步验证了其靶点,为深入阐明黑果枸杞总黄酮的药效物质基础及作用机制提供了实验及理论依据。

关键词: 非酒精性脂肪肝疾病, 黑果枸杞总黄酮, 生物信息分析, 差异表达基因, WGCNA, UPLC/MS-MS

Abstract:

Purport based on bioinformatics analysis revealed the key gene of nonalcoholic fatty liver disease and based on ultra-high performance liquid chromatography-mass spectrometry (UPLC/MS-MS) technology,bioinformatics,and molecular docking to identify and explore the Lycium ruthenicum Murr. flavonoids compounds and treatment of nonalcoholic fatty liver disease (NAFLD) the mechanism of action,provide a reference basis for the research of its efficacy material base.This study used the GSE89632 dataset,which included 39 patients with NAFLD and 24 control patients.3 375 differential genes were obtained by Limma packet analysis,and 19 modules and 95 most relevant genes were obtained by WGCNA analysis.Through qualitative analysis and target prediction,71 active components and 375 related genes were obtained.24 genes were obtained from the intersection of disease genes and component target genes.Top 10 hub genes were screened out by CytoHubba.Nine KEGG channels and 33 GO analysis items were obtained through David database.Molecular docking results showed that most total flavonoids of L. ruthenicum had good binding ability with key targets.The results of survival analysis showed that VEGFA and HCC survival analysis were closely related.The hub gene was associated with eight types of immune cells,including juvenile B cells,γδT cells and monocytes.This study reveals the key gene of nonalcoholic fatty liver disease,has been clear about the L. ruthenicum  flavonoids ingredients,forecasts the L. ruthenicum  flavone component in the treatment of non-alcoholic fatty liver disease and the mechanism of action of preliminary verified its targets,to further clarify the L. ruthenicum  medicinal material basis and mechanism of total flavonoids provides experimental and theoretical basis.

Key words: non-alcoholic fatty liver disease, total flavonoids of Lycium ruthenicum Murr., differentially expressed genes, WGCNA, UPLC/MS-MS, bioinformatics analysis

中图分类号:  R285