滨州医学院学报2024,Vol.47Issue(2) :142-146.DOI:10.19739/j.cnki.issn1001-9510.2024.02.013

基于网络药理学和实验验证四君子汤治疗阿尔茨海默病的作用机制

Mechanism of Sijunzi Decoction in treatment of Alzheimer's Disease:based on network pharmacology and in vitro experimental verification

王彦君 张清 马辉 许勇 孟渝涵 靳若艺 李晓莉 叶蕾
滨州医学院学报2024,Vol.47Issue(2) :142-146.DOI:10.19739/j.cnki.issn1001-9510.2024.02.013

基于网络药理学和实验验证四君子汤治疗阿尔茨海默病的作用机制

Mechanism of Sijunzi Decoction in treatment of Alzheimer's Disease:based on network pharmacology and in vitro experimental verification

王彦君 1张清 1马辉 1许勇 1孟渝涵 1靳若艺 1李晓莉 1叶蕾1
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作者信息

  • 1. 滨州医学院 山东 烟台 264003
  • 折叠

摘要

目的 利用网络药理学和实验验证四君子汤治疗阿尔茨海默病(AD)的潜在作用机制.方法 通过中药系统药理学数据库与分析平台(TCMSP)检索四君子汤的有效成分及相关靶点,采用DisGeNET和GeneCards 数据库搜集AD靶点.采用String数据库建立其共有靶点蛋白互作(PPI)网络,并运用Cytoscape软件绘制"药物-活性成分-作用靶点-疾病"网络.采用DAVID对关键靶点进行基因本体(GO)和基因组百科全书(KEGG)富集分析.取 24 只 3 月龄SPF级APP/PS1 双转基因雄性小鼠随机分为模型组和低、高剂量四君子汤实验组,另取 8 只C57BL/6 小鼠作为阴性对照组.低、高剂量实验组连续灌胃四个月.采用Morris水迷宫实验检测小鼠记忆能力和空间探索能力,采用相关试剂盒检测超氧化物歧化酶(SOD)、乙酰胆碱酯酶(AChE)、丙二醛(MDA)等氧化应激指标水平,电镜检测脑组织病理学变化.结果 最终筛选出四君子汤 128 个有效成分,并得到与AD共有靶点 49 个,其中以 AKT1、Caspase-3(Casp3)、TNF 等为核心靶点,与PI3K-Akt信号通路密切相关.动物实验证实,动物实验可改善小鼠认知功能,病理结果显示四君子汤能减轻其中线粒体损伤,生化指标显示四君子汤可提高小鼠脑内AChE水平,降低SOD、MDA水平.结论 四君子汤可以减轻APP/PS1 引起的小鼠认知功能改变、脑内病理变化及生化指标的变化,为进一步阐释其物质基础和机制提供依据.

Abstract

Objective To investigate the potential mechanism of Sijunzi Decoction in treating Alzheimer's disease(AD)by network pharmacology and experiments.Methods The effective components and related targets of Sijunzi Decoction were re-trieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),while DisGeNET and GeneCards Databases were used to collect AD targets.The common target protein-protein interaction(PPI)network was es-tablished by String database,and the'drug-active ingredient-target-disease'network was drawn by Cytoscape software.Gene On-tology(GO)term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of key tar-gets was performed using Database for Annotation,Visualization and Integrated Discovery(DAVID).Twenty-four 3-month-old SPF APP/PS1 double transgenic male mice were randomly divided into the model group,the low-dose and high-dose experimental groups,and 8 C57BL6 mice were used as the negative control group.Low and high dose experimental groups were fed for four months.Morris water maze test was used to detect the memory ability and space exploration ability of mice,and the oxidative stress indexes such as superoxide dismutase(SOD),acetylcholinesterase(AChE)and malonaldehyde(MDA)were detected by relevant kits.The pathological changes of brain were detected by electron microscopy.Results Finally,128 active components of Sijunzi Decoction were screened out,and 49 common targets with AD were obtained.Among them,AKT1,Caspase-3(Casp3)and TNF were the core targets,which were closely related to PI3K-Akt signaling pathway.Animal experiments confirmed that an-imal experiments could improve the cognitive function of mice,pathological results showed that Sijunzi decoction could alleviate the mitochondrial damage,and biochemical indicators showed that Sijunzi decoction could increase the AChE level in the brain of mice and reduce the SOD and MDA levels.Conclusion Sijunzi Decoction can alleviate the cognitive function changes,brain pathological changes and biochemical changes induced by APP/PS1 in mice,and provide a basis for further explanation of its ma-terial basis and mechanism.

关键词

四君子汤/阿尔兹海默症/网络药理学/氧化应激

Key words

Sijunzi Decoction/Alzheimer's disease/network pharmacology/oxidative stress

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基金项目

烟台市重点研发计划(2019XDHZ107)

山东省大学生创新创业训练计划(S202110440022)

滨州医学院大学生创新创业训练计划(X202210440328)

出版年

2024
滨州医学院学报
滨州医学院

滨州医学院学报

影响因子:0.548
ISSN:1001-9510
参考文献量25
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