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龙清吟,傅馨莹,李菀榆,李俊熙,刘竞泽,李艳军,谭维,胡聪,张伟.补阳还五汤抗动脉粥样硬化氧化应激的生信分析及实验研究[J].湖南中医药大学学报英文版,2023,43(4):668-676.[Click to copy
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| 补阳还五汤抗动脉粥样硬化氧化应激的生信分析及实验研究 |
| 龙清吟,傅馨莹,李菀榆,李俊熙,刘竞泽,李艳军,谭维,胡聪,张伟 |
| (湖南中医药大学中西医结合心脑疾病防治湖南省重点实验室, 湖南 长沙 410208) |
| 摘要: |
| 目的 基于基因芯片数据库（GEO）、网络药理学，结合ox-LDL诱导的大鼠主动脉血管内皮细胞氧化损伤模型进行实验验证，探究补阳还五汤（Buyang Huanwu Decoction, BYHWD）干预动脉粥样硬化（atherosclerosis, AS）氧化应激的作用及相关机制。方法 通过TCMSP、Herb数据库收集BYHWD中7味中药有效成分及靶点；从GEO数据库下载GSE19286、GSE2372数据集，鉴定AS差异表达基因（differentially expressed genes, DEGs）；通过GeneCards数据库获取氧化应激靶点；取交集筛选出BYHWD、DEGs、氧化应激共同靶点，进行PPI、GO和KEGG通路富集分析；在GSE19286、GSE2372的表达矩阵中，采用独立样本t检验进行核心靶点验证。结合GEO数据库和网络药理学结果进行体外实验验证，检测药物对细胞活性氧表达及ALB、PLG、F2、GC、PLK1基因表达的影响。结果 筛选出972个中药靶点、9438个氧化应激靶点、173个DEGs，其中103个DEGs在AS组织样本中高表达、70个DEGs在AS组织样本中低表达；综合中药作用靶点、AS DEGs和氧化应激靶点，得到24个“AS潜在靶点”，进行GO和KEGG富集分析，结果提示“AS潜在靶点”主要通过调控细胞周期信号通路，卵母细胞成熟信号通路和细胞减数分裂信号通路等信号通路发挥作用。根据Degree算法对“AS潜在靶点”进行拓扑分析，鉴定出前5位“AS核心靶点”，据统计分析提示BYHWD可能可以通过上调ALB、PLG、F2、GC的表达、下调PLK1的表达起到干预AS氧化应激的作用。体外实验结果显示，BYHWD能抑制ox-LDL引起的活性氧（reactive oxygen species, ROS）增高；qPCR结果显示，ox-LDL刺激后的大鼠主动脉内皮细胞ALB、PLG、F2、GC基因表达均下降，PLK1基因表达上升，BYHWD含药血清干预后可以上调ALB、PLG、F2、GC基因的表达（P<0.01；P<0.05），下调PLK1的表达（P<0.05）。结论 BYHWD干预AS氧化应激具有多成分、多靶点、多途径的作用特点，其机制可能与减少ROS表达，上调ALB、PLG、F2、GC基因、下调PLK1基因表达相关。 |
| 关键词: 补阳还五汤 动脉粥样硬化 氧化应激 基因芯片 网络药理学 分子对接 |
| DOI：10.3969/j.issn.1674-070X.2023.04.016 |
| Received:November 23, 2022 |
| 基金项目:国家自然科学基金项目（82174218）；湖南省自然科学杰出青年基金项目（2020JJ2024）；湖南中医药大学中西结合一流学科开放基金项目（2020ZXYJH49）。 |
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| Bioanalysis and experimental study of Buyang Huanwu Decoction against oxidative stress in atherosclerosis |
| LONG Qingyin,FU Xinying,LI Wanyu,LI Junxi,LIU Jingze,LI Yanjun,TAN Wei,HU Cong,ZHANG Wei |
| (College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To investigate the interventions of Buyang Huanwu Decoction (BYHWD) on atherosclerosis (AS) oxidative stress and its related mechanism using Gene Expression Omnibus (GEO) and network pharmacology, combined with the rat aortic vascular endothelial cell oxidative damage model induced by ox-LDL.Methods The active components and targets of 7 Chinese medicines in BYHWD were collected by TCMSP and Herb. GSE19286 and GSE2372 data sets were downloaded from GEO to identify AS differentially expressed genes (DEGs). The oxidative stress (OS) targets were obtained from GeneCards database. The common targets of BYHWD, DEGs and OS were selected by intersection to analyze the enrichment of PPI, GO and KEGG pathways. In the expression matrix of GSE19286 and GSE2372, the core target was verified by independent sample t-test. The effects of drugs on the expression of reactive oxygen species and the expression of ALB, PLG, F2, GC and PLK1 genes were tested in vitro combined with GEO and network pharmacological results.Results The total of 972 TCM targets, 9438 OS targets, and 173 DEGs were screened. Among them, 103 DEGs were highly expressed and 70 DEGs were lowly expressed in AS tissue samples. By combining the BYHWD targets, ASDEGS and OS targets, 24 "AS potential targets" were obtained for GO and KEGG enrichment analysis. The results suggested that "AS potential targets" mainly play a role by regulating cell cycle, oocyte maturation and cell meiosis signaling pathways. According to the topological analysis of "AS potential target" based on Degree algorithm, the five "AS core targets" were identified. According to statistical analysis, BYHWD may interfere with AS OS by up-regulating the expression of ALB, PLG, F2, GC and down-regulating the expression of PLK1. The results of vitro experiment showed that BYHWD could inhibit the increase of reactive oxygen species (ROS) induced by ox-LDL. The qPCR results showed that the expression of ALB, PLG, F2 and GC gene decreased and the expression of PLK1 gene increased in rat aortic endothelial cells stimulated by ox-LDL. BYHWD-containing serum could up-regulate the expression of ALB, PLG, F2 and GC (P<0.01, P<0.05) and down-regulate the expression of PLK1 (P<0.05).Conclusion BYHWD has the characteristics of multi-component, multi-target and multi-pathway in the intervention of atherosclerotic OS, and its mechanism may be related to the decrease of ROS expression, up-regulation of ALB, PLG, F2, GC gene and down-regulation of PLK1 gene expression. |
| Key words: Buyang Huanwu Decoction atherosclerosis oxidative stress gene chip network pharmacology molecular docking |
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