Zhu Yanfang, Zhu Haoyan, Zhou Jia, Wu Jiahe, Hu Xiaorong, Li Chenze, Cai Huanhuan, Lu Zhibing
Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Institute of Myocardial Injury and Repair, Wuhan University, Wuhan 430071, China.
Biomedicines. 2025 Aug 29;13(9):2114. doi: 10.3390/biomedicines13092114.
: Cardiomyocyte death is a key factor in myocardial ischemia-reperfusion injury (MI/RI), and the expression patterns and molecular mechanisms of pyroptosis-related genes (PRGs) in ischemia-reperfusion injury are poorly understood. : The mouse MI/RI injury-related datasets GSE61592 and GSE160516 were obtained from the Gene Expression Omnibus database, and differential expression analysis was performed on each to identify differentially expressed genes (DEGs). The DEGs were intersected with the PRGs obtained from GeneCards to identify differentially expressed PRGs in MI/RI. Enrichment analysis identified key pathways, while PPI network analysis revealed hub genes. The expression patterns and immune cell infiltration of hub genes were also investigated. The molecular docking prediction of key genes was performed using MOE software in conjunction with the ZINC small molecular compounds database. Key gene expression was validated in an external dataset (GSE4105), a mouse MI/RI model, and an HL-1 cell hypoxia/reoxygenation model via RT-qPCR. : A total of 29 differentially expressed PRGs were identified, which are primarily associated with pathways such as "immune system process", "response to stress", "identical protein binding", and "extracellular region". Seven key genes (, , , , , , ) were screened, all strongly correlated with immune infiltration. Seven FDA-approved small molecule compounds exhibiting the highest docking potential with each key gene were selected based on a comprehensive evaluation of S-scores and hydrogen bond binding energies. , , and were successfully validated across external datasets, the mouse MI/RI model, and the cardiomyocyte H/R model. : , , and may be key genes involved in MI/RI-related pyroptosis. Targeting these genes may provide new insights into the treatment of MI/RI.
心肌细胞死亡是心肌缺血再灌注损伤（MI/RI）的关键因素，而缺血再灌注损伤中焦亡相关基因（PRGs）的表达模式和分子机制尚不清楚。从小鼠MI/RI损伤相关数据集GSE61592和GSE160516中获取基因表达综合数据库，并对每个数据集进行差异表达分析，以识别差异表达基因（DEGs）。将DEGs与从GeneCards获得的PRGs进行交叉分析，以识别MI/RI中差异表达的PRGs。富集分析确定关键途径，而蛋白质-蛋白质相互作用（PPI）网络分析揭示枢纽基因。还研究了枢纽基因的表达模式和免疫细胞浸润情况。使用MOE软件结合ZINC小分子化合物数据库对关键基因进行分子对接预测。通过逆转录定量聚合酶链反应（RT-qPCR）在外部数据集（GSE4105）、小鼠MI/RI模型和HL-1细胞缺氧/复氧模型中验证关键基因的表达。共鉴定出29个差异表达的PRGs，它们主要与“免疫系统过程”、“应激反应”、“相同蛋白质结合”和“细胞外区域”等途径相关。筛选出7个关键基因（……），均与免疫浸润密切相关。基于对S评分和氢键结合能的综合评估，选择了7种美国食品药品监督管理局（FDA）批准的与每个关键基因具有最高对接潜力的小分子化合物。……在外部数据集、小鼠MI/RI模型和心肌细胞缺氧/复氧模型中均成功得到验证。……可能是参与MI/RI相关焦亡的关键基因。靶向这些基因可能为MI/RI的治疗提供新的见解。
