首页|基于网络药理学与GEO差异基因芯片数据探讨芦丁治疗脊髓损伤的作用机制

基于网络药理学与GEO差异基因芯片数据探讨芦丁治疗脊髓损伤的作用机制

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为了探究芦丁治疗脊髓损伤的作用机制,基于网络药理学和GEO差异基因芯片数据分析,结合体内实验,筛选芦丁对脊髓损伤的作用靶点。首先通过TCMSP、Swiss Target Prediction和SuperPred数据库获得芦丁的作用靶点,同时采用GEO差异基因、CTD、OMIM、PharmGkb疾病数据库获取脊髓损伤的疾病靶点;然后应用Cytoscape软件采用蛋白互作的方式筛选芦丁治疗脊髓损伤的核心靶点,并采用R语言对核心靶点进行GO功能及KEGG通路富集分析;最后采用Rutgers MASCIS脊髓损伤撞击器建立大鼠急性脊髓损伤模型,芦丁干预 3d后采用BBB运动评分法对大鼠后肢运动功能进行评价,采用酶联免疫吸附测定法检测脊髓中炎症因子TNF-α、IL-6、IL-1β和NF-κB的表达水平以及ROS和MDA含量。结果发现:①芦丁共有 56 个对应的蛋白靶点,脊髓损伤筛选到 4 624 个疾病靶点,合并后得到 5 个核心靶点,即CASP3、ESR1、GSK3B、IL-6、MTOR;②GO功能主要集中在对氧化应激的反应、活性氧代谢过程、NF-κB结合等,KEGG通路分析显示,芦丁治疗脊髓损伤相关的通路包括PI3K-Akt信号通路、AMPK信号通路、HIF-1 信号通路等;③分子对接实验和分子动力学模拟表明,芦丁与 5 个核心靶点均有良好且稳定的结合;④体内实验结果显示,脊髓损伤后使用芦丁进行药物干预处理可以降低脊髓的含水量,减少炎性因子和氧化应激因子的产生。上述结果证实,芦丁可以通过多个靶点以及多条通路在治疗脊髓损伤中发挥抗炎和抗氧化作用。
Molecular mechanism of rutin treatment for spinal cord injury based on network pharmacology and GEO differential gene chip data analysis
To explore the mechanism of rutin in the treatment of spinal cord injury(SCI),the targets of rutin in the treatment of SCI were screened based on network pharmacology and GEO differential gene chip data analysis combined with in vivo experi-ments.Firstly,the targets of rutin were obtained through TCMSP,Swiss Target Prediction,and SuperPred databases,and the disease targets for SCI were obtained through GEO differentially expressed genes,CTD,OMIM,and PharmaGkb disease databases.Then,Cytoscape software was used to screen the core targets of rutin for SCI by protein interaction,and R language was used to analyze the GO function and KEGG pathway enrichment of the core targets.Finally,a model of acute SCI in rat was established using Rutgers MASCIS SCI impactor,and the BBB motor score method was used to evaluate the hind limb motor function of rats after three days of intervention with rutin.The expression levels of TNF-α,IL-6,il-1β,NF-κb,and the contents of ROS and MDA in spinal cord homogenate were detected by enzyme-linked immunosorbent assay(Elisa).The results are as follows:①There are 56 cor-responding protein targets in rutin and 4 624 disease targets for SCI,and five core targets were obtained after merging,namely CASP3,ESR1,GSK3B,IL-6,MTOR;②GO function mainly focuses on the response to oxidative stress,reactive oxygen species metabolism process,NF-κB binding,etc.PI3K-Akt signaling pathway,AMPK signaling pathway,HIF-1 signaling pathway,etc.were involved in rutin treatment of spinal cord injury by KEGG pathway analysis;③Molecular docking experiments and molecular dynamics simulations show that rutin has good and stable binding with five core targets;④The results of in vivo experiments indicate that drug intervention with rutin after SCI can reduce the water content in the spinal cord,and reduce the production of inflammatory factors and oxidative stress factors.These results demonstrate that rutin has anti-inflammatory and anti-oxidative effects in the treatment of SCI through multiple targets and pathway.

network pharmacologyGEO differential gene chiprutinspinal cord injurymolecular dockingin vivo experiments

周亚净、段春胜、何润之、程芳、吴黎莉、刘建敏

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邢台市人民医院麻醉科,河北 邢台 054001

邢台市人民医院小儿外科,河北 邢台 054001

邢台市人民医院神经外科,河北 邢台 054001

邢台市人民医院皮肤科,河北 邢台 054001

中国医学科学院皮肤科研究所 药研室,南京 210042

邢台市人民医院手足外科,河北 邢台 054001

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网络药理学 GEO差异基因芯片 芦丁 脊髓损伤 分子对接 体内实验

邢台市科技局项目

2020zc233

2024

天津师范大学学报(自然科学版)
天津师范大学

天津师范大学学报(自然科学版)

CSTPCD北大核心
影响因子:0.311
ISSN:1671-1114
年,卷(期):2024.44(3)
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