Table 1_Identification of diagnostic genes for myocardial ischemia reperfusion injury associated with metabolic syndrome through the integration of bioinformatics analysis, molecular docking and experimental validation.xlsx

BackgroundMetabolic dysregulation in metabolic syndrome (MetS) exacerbates myocardial ischemia-reperfusion injury (MIRI). This study aimed to identify diagnostic biomarkers and therapeutic candidates for MetS-associated MIRI.
MethodsThree MIRI and two MetS datasets from GEO were analyzed using differential expression analysis, WGCNA, and machine learning (LASSO/SVM-RFE). Hub genes were validated via qRT-PCR in hypoxia-induced H9C2 cells. Drug candidates were predicted via PPI networks, CTD, and molecular docking, followed by experimental evaluation of dexamethasone.
ResultsFive hub genes—DAK, GTF3C5, KCNMB1, TRAF1, and ZNF692—were identified, with distinct expression patterns (DAK/GTF3C5 downregulated; KCNMB1/TRAF1/ZNF692 upregulated). These genes were enriched in immune-related pathways, and their diagnostic performance was robust (AUCs: 0.875–0.969). Dexamethasone downregulated KCNMB1/TRAF1/ZNF692 and reduced apoptosis in H9C2 cells.
ConclusionThis study reveals immune-metabolic dysregulation as a key driver of MetS-MIRI, proposes five biomarkers for diagnosis, and highlights dexamethasone as a promising therapeutic candidate.

背景 代谢综合征（Metabolic Syndrome, MetS）所伴随的代谢失调会加剧心肌缺血再灌注损伤（Myocardial Ischemia-Reperfusion Injury, MIRI）。本研究旨在筛选与代谢综合征相关心肌缺血再灌注损伤的诊断生物标志物及治疗候选药物。
方法 从基因表达综合数据库（Gene Expression Omnibus, GEO）获取3个心肌缺血再灌注损伤数据集与2个代谢综合征数据集，采用差异表达分析、加权基因共表达网络分析（Weighted Gene Co-expression Network Analysis, WGCNA）以及机器学习方法（最小绝对收缩和选择算子/支持向量机-递归特征消除，LASSO/SVM-RFE）开展数据分析。通过实时荧光定量聚合酶链反应（quantitative real-time polymerase chain reaction, qRT-PCR）验证核心基因在缺氧诱导的H9C2细胞中的表达水平。借助蛋白质相互作用网络（Protein-Protein Interaction, PPI）、比较毒理基因组学数据库（Comparative Toxicogenomics Database, CTD）与分子对接技术预测候选治疗药物，并对地塞米松进行实验验证。
结果 本研究共鉴定出5个核心基因：DAK、GTF3C5、KCNMB1、TRAF1及ZNF692，其表达模式存在显著差异（DAK/GTF3C5表达下调；KCNMB1/TRAF1/ZNF692表达上调）。上述基因显著富集于免疫相关通路，且具备优异的诊断效能（受试者工作特征曲线下面积（Area Under the Curve, AUC）：0.875~0.969）。实验结果显示，地塞米松可下调KCNMB1、TRAF1及ZNF692的表达，并降低缺氧诱导H9C2细胞的凋亡水平。
结论 本研究揭示免疫代谢失调是代谢综合征相关心肌缺血再灌注损伤的关键驱动因素，提出5个可用于临床诊断的生物标志物，并证实地塞米松为极具潜力的治疗候选药物。