天香丹调节线粒体能量代谢治疗心肌缺血损伤的作用机制研究  

Research on the mechanism of Tianxiangdan regulating mitochondrial energy metabolism in treating myocardial ischemic injury

作　　者：郭闫闫 赵明芬[2] 侯晓叶 袁茜茜 GUO Yanyan;ZHAO Mingfen;HOU Xiaoye;YUAN Xixi(The Fourth Clinical Medical College of Xinjiang Medical University,Urumqi 830000,China;Cadre Department of Xinjiang Medical University Affiliated Traditional Chinese Medicine Hospital,Urumqi 830000,China)

机构地区：[1]新疆医科大学第四临床医学院,新疆乌鲁木齐830000 [2]新疆医科大学附属中医医院,新疆乌鲁木齐830000

出　　处：《海南医学院学报》2024年第24期1876-1886,共11页Journal of Hainan Medical University

基　　金：2024年新疆维吾尔自治区研究生创新项目(XJ2024G162);国家自然科学基金资助项目(82160876)。

摘　　要：目的:通过生物信息学、网络药理学、免疫浸润分析和分子对接技术,筛选心肌缺血损伤线粒体能量代谢相关基因,揭示天香丹治疗心肌缺血损伤的作用机制是否与调控线粒体能量代谢相关。方法:通过网络药理学、生物信息学筛选“天香丹-心肌缺血再灌注损伤-线粒体能量代谢”差异表达基因(DEGs)并分析其相关性。对线粒体能量代谢DEGs进行基因富集分析,通过构建蛋白质相互作用(PPI)网络,筛选心肌缺血再灌注损伤潜在线粒体能量代谢的关键(Hub)基因。通过数据集的免疫细胞和免疫功能打分,评估免疫细胞浸润水平,并对关键基因分别进行免疫浸润分析及基因集富集分析(GSEA)。而后,为研究线粒体能量代谢DEGs和高风险因子间的相互关系,开展线粒体能量代谢DEGs与风险因子的相关性分析。并运用分子对接技术验证重要成分和关键分子靶点间的相互作用。最后,采用动物实验再次验证关键基因GNAI2、Mfn2是否是天香丹调节线粒体能量代谢治疗心肌缺血损伤的关键分子靶点。结果:经筛选共得到“天香丹-心肌缺血再灌注损伤-线粒体能量代谢”差异表达基因24个,相关性分析发现关键基因间表现出较强的协同作用。基因富集结果发现关键基因间具有相互调控、调节免疫作用和介导多条信号通路的作用。通过PPI网络筛选得到与心肌缺血损伤潜在线粒体能量代谢密切相关的10个Hub基因,并且这些关键基因在免疫浸润分析及GSEA富集分析中均显示出与免疫过程和炎症反应间的较强相关性。最后,关键基因的风险因子相关性分析结果验证了上述基因对心肌缺血损伤疾病的临床预测效能。结论:天香丹调节线粒体能量代谢治疗心肌缺血损伤可能与GNAI2、Mfn2等关键分子靶点及其介导的TNF信号通路、cAMP信号通路等多条信号通路和免疫调节机制密切相关。Objective:To screen mitochondrial energy metabolism related genes in myocardial ischemic injury through bioinformatics,network pharmacology,immune infiltration analysis,and molecular docking techniques,and to reveal whether the mechanism of Tianxiangdan in treating myocardial ischemic injury is related to regulating mitochondrial energy metabolism.Methods:Differential expression genes(DEGs)of"Tianxiangdan myocardial ischemia-reperfusion injury mitochondrial energy metabolism"were screened through network pharmacology and bioinformatics,and their correlation was analyzed.Gene enrichment analysis was performed on mitochondrial energy metabolism DEGs,and a protein-protein interaction(PPI)network was constructed to screen for potential key(Hub)genes involved in mitochondrial energy metabolism in myocardial ischemia-reperfusion injury.By scoring the immune cells and immune function of the gene set,evaluate the level of immune cell infiltration,and perform immune infiltration analysis and gene set enrichment analysis(GSEA)on key genes separately.Subsequently,in order to investigate the relationship between mitochondrial energy metabolism DEGs and high-risk factors,a correlation analysis was conducted between mitochondrial energy metabolism DEGs and risk factors.Molecular docking technology was used to verify the interactions between important components and key molecular targets.Finally,animal experiments were conducted to further verify whether the key genes GNAI2,Mfn2 are the key molecular targets of Tianxiangdan in regulating mitochondrial energy metabolism for the treatment of myocardial ischemic injury.Results:After screening,a total of 24 differentially expressed genes were identified for"Tianxiangdan myocardial ischemia-reperfusion injury mitochondrial energy metabolism".Correlation analysis revealed strong synergistic effects among key genes.The gene enrichment results revealed that key genes have the functions of mutual regulation,immune regulation,and mediating multiple signaling pathways.Ten Hub genes closel

关 键 词：天香丹 心肌缺血损伤 线粒体能量代谢 机制研究 实验验证 

分 类 号：R285[医药卫生—中药学]