基于生物信息学探究枸杞子治疗阿尔茨海默病的分子机制  

Exploration of Molecular Mechanism of Fructus Lycii in Treatment of Alzheimer′s Disease Based on Bioinformatics

作　　者：于杰[1] 赵忠阳[2] 闫薇[2] 魏成群 YU Jie;ZHAO Zhongyang;YAN Wei;WEI Chengqun(Department of Geriatric Neurology,Heilongjiang Provincial Hospital,Harbin 150005,China;Department of Cardiovascular Medicine,the First Affiliated Hospital of Harbin Medical University,Harbin 150001,China;Department of Neurology,Huai′an Huai′an Hospital/Huai′an Cancer Hospital,Huai′an 223200,China)

机构地区：[1]黑龙江省医院老年神经内科,哈尔滨150005 [2]哈尔滨医科大学附属第一医院心血管内科,哈尔滨150001 [3]淮安市淮安医院淮安市肿瘤医院神经内科,江苏淮安223200

出　　处：《医学综述》2024年第19期2418-2426,共9页Medical Recapitulate

基　　金：黑龙江省中医药科研项目(ZHY2022-058)。

摘　　要：目的基于生物信息学揭示枸杞子治疗阿尔茨海默病(AD)的潜在靶点,探讨其相关生物学机制。方法通过检索中药系统药理学数据库和分析平台(TCMSP)获得枸杞子的活性成分及其潜在靶点,通过基因-疾病关联数据库(DisGeNET)检索AD相关基因靶标。将枸杞子活性成分的潜在靶点和AD相关基因交集后的靶基因,导入功能性蛋白质关联网络数据库(STRING)构建蛋白质-蛋白质相互作用网络,鉴定出关键靶点,进一步构建靶点-通路-疾病的相互作用网络,同时对基因本体论(GO)通路和京都基因与基因组百科全书(KEGG)通路进行富集分析。利用Cytoscape 3.7.1建立成分-靶点-通路-疾病网络。采用AutoDockVina软件进行分子对接并计算结合亲和力。结果从枸杞子中筛选得到36种相关成分,对应靶点202个。从DisGeNET数据库中收集了123个与AD相关的重要基因,最终确定了28个活性枸杞子成分和AD的共享靶点,其中10个靶点:肿瘤坏死因子、白细胞介素(IL)-6、胱天蛋白酶3、血管内皮生长因子A、前列腺素内过氧化物合酶2、超氧化物歧化酶1、IL-1B、淀粉样前体蛋白、过氧化物酶体增殖物激活受体γ、血红素加氧酶1,通过最大团节点中心性算法进一步定义为关键基因靶点。在P<0.01的条件下,GO途径的富集分析分别证明了10个生物学过程、分子功能和细胞成分。KEGG通路富集分析得到102条P<0.05的通路。分子对接显示,槲皮素、甘氨酸、β-谷甾醇等具有较高的亲和力,可以成为治疗AD的潜在药物。结论枸杞子治疗AD的机制与细胞凋亡、神经炎症、神经退行性病变等途径有关,可为枸杞子治疗AD提供药理学依据。Objective To uncover the potential targets and clarify the related biological mechanisms of Lycii fructus(LF,Gouqizi,)in treating Alzheimer′s disease(AD)based on bioinformatics.Methods The active ingredients and potential targets of LF were obtained by searching on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).Targets of AD related genes were retrieved through the database of gene-disease associations(DisGeNET).The potential targets of active ingredients in LF were intersected with AD related genes,and the target genes were imported into the Functional Protein Association Network Database(STRING)to construct a protein-protein interaction network.Key targets were identified,and a target-pathway-disease interaction network was further constructed.At the same time,the enrichment analysis of the Gene Ontology(GO)pathway and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway were performed.A component-target-pathway-disease network was established by using Cytoscape 3.7.1.AutoDockVina software was adopted for molecular docking and calculating binding affinity.Results 36 related ingredients with 202 corresponding targets were selected and obtained from LF.123 important genes correlated to AD were collected from the DisGeNET database.Then,a total of 28 shared targets of active LF constituents and AD were eventually identified,among which 10 targets[tumor necrosis factor,interleukin(IL)-6,caspase-3,vascular endothelial growth factor A,prostaglandin-endoperoxide synthase 2,superoxide dismutase 1,IL-1B,amyloid precursor protein,peroxisome proliferator-activated receptorγ,heme oxygenase 1]were further defined as key gene targets by using the maximal clique centrality algorithm.Enrichment analysis of GO pathway demonstrated 10 biological processes,molecular functions,and cell components respectively on condition that P<0.01.102 pathways with P<0.05 were obtained from KEGG pathway enrichment analysis.Molecular docking showed that quercetin,glycitein andβ-sitosterol had a hig

关 键 词：阿尔茨海默病 枸杞子 网络药理学 

分 类 号：R285[医药卫生—中药学]