三叶豆苷调控多通路减轻心肌梗死后心肌细胞氧化应激损伤和凋亡的机制研究
Mechanism of Trifolin in alleviating oxidative stress damage and apoptosis of cardiac myocyte after myocardial infarction
郭智 1吴美珠 1林国晟 1程瑛 1郑慧芳 1彭军 1沈阿灵1
作者信息
- 1. 福建中医药大学中西医结合研究院,福州 350122;福建省中西医结合老年性疾病重点实验室,福州 350122
- 折叠
摘要
目的:通过高通量基因数据库(GEO)芯片和网络药理学方法探讨三叶豆苷对心肌梗死(MI)的潜在治疗作用、靶点及通路,并通过体外实验验证三叶豆苷干预对缺血缺氧条件下心肌细胞凋亡的影响及对相关通路的调控作用.方法:通过GEO数据平台、网络药理学分析三叶豆苷治疗MI的潜在靶点,通过GO和KEGG分析富集潜在相关通路,并通过缺血缺氧诱导H9C2构建体外细胞模型,验证三叶豆苷干预对氧化应激、凋亡及潜在富集通路活化的影响.结果:通过GEO数据集发现MI小鼠中有668个基因上调和651个基因下调,通过多个数据库获取三叶豆苷472个潜在作用靶点,从而获取49个交集靶点,且与BCL2L1、PIK3CA等靶点密切相关.通过GO分析发现,凋亡过程的负调控、炎症反应调节等过程被显著富集.通过KEGG分析发现,PI3K/Akt、HIF-1等通路被显著富集.体外实验结果表明,三叶豆苷干预可抑制缺血缺氧诱导后H9C2的细胞凋亡、线粒体膜电位的下调、ROS的生成、HIF-1α和NOX4蛋白的表达及PI3K/Akt和MAPK通路的异常活化.结论:三叶豆苷抑制缺血缺氧诱导后H9C2细胞的氧化应激损伤、线粒体膜电位改变及凋亡、通过调控PI3K/Akt和MAPK通路,可能是其抗MI的重要机制之一.
Abstract
Objective:Gene Expression Omnibus(GEO)database and network pharmacology methods were performed to explore the potential therapeutic effects,targets,and pathways of trifolin on myocardial infarction,and verifying the effects of trifolin treatment on ischemia and hypoxia-induced cardiomyocyte apoptosis and its regulatory mechanism in vitro.Methods:GEO data platform and network pharmacology analysis were performed to investigate the potential targets of trifolin for treating myocardial infarction.GO and KEGG analysis were performed to enriches potential related pathways.By inducing ischemia and hypoxia in H9C2 cells to establish an in vitro cell model,the study validates the effects of trifloin treatment on oxidative stress,apoptosis,and the activation of potential enriched pathways.Results:Analysis of the GEO dataset revealed 668 up-regulated and 651 down-regulated genes in myocardial infarction mice.A total of 472 potential target genes of trifolin were identified from diverse databases,yielding 49 overlapping target genes associated with BCL2L1 and PIK3CA.Negative regulation of the apoptosis process and inflammatory response,among other processes,are notably enriched through GO analysis.Similarly,KEGG analysis shows significant enrichment in pathways like PI3K/Akt and HIF-1.The in vitro experimental results indicated that trifolin treatment inhibited cell apoptosis,mitochondrial membrane potential downregulation,ROS generation,protein expression of HIF-1α and NOX4,as well as abnormal activation of the PI3K/Akt and MAPK pathways in ischemia and hypoxia-induced H9C2.Conclusion:Trifolin suppressed oxidative stress-induced damage,alteration in mitochondrial membrane potential,apoptosis in ischemia and hypoxia-induced H9C2,and regulated the PI3K/Akt and MAPK pathways,which may be one of its important mechanisms for anti-myocardial infarction.
关键词
网络药理学/三叶豆苷/心肌梗死/心肌细胞凋亡/氧化应激Key words
Pharmacology network/Trifolin/Myocardial infarction/Cardiomyocyte apoptosis/Oxidative stress引用本文复制引用
基金项目
国家自然科学基金(U22A20372)
国家自然科学基金(82074363)
福建省科技重大专项(2019YZ014004)
福建省卫生健康中青年领军人才项目()
中华中医药学会青年人才托举工程项目(2021-2023)(2021-QNRC2-B19)
福建中医药大学青年科研拔尖人才项目(XQB202202)
出版年
2024
NETL
NSTL
万方数据