摘要
目的通过蛋白质组学、数据挖掘和生物信息学的综合分析,识别致死性心律失常相关心源性猝死的关键蛋白质,并探究其潜在分子机制。方法使用8周龄雄性SD大鼠构建致死性心律失常模型,分为心律失常组和对照组。运用蛋白质组学技术对左心室心肌组织进行蛋白质鉴定与定量分析,并筛选与心律失常相关的差异表达蛋白质。通过比对数据库中的目标基因蛋白质,并进行联合分析,以进一步识别关键蛋白质,同时利用生物信息学方法深入探索其潜在的分子机制。结果成功鉴定出356种差异表达蛋白质,其中189种上调,167种下调。通过与目标基因蛋白质的关联分析,筛选出71种关键蛋白质,并构建了蛋白质互作网络。GO富集分析和KEGG富集分析结果显示,这些关键蛋白质主要涉及离子通道功能异常、氧化应激增加和自主神经调节失衡等潜在的分子机制。结论本研究通过蛋白质组学、数据挖掘和生物信息学的方法,揭示了致死性心律失常相关心源性猝死中的关键分子机制,为法医学鉴定及死亡机制研究提供了新的视角和潜在的生物标志物。
Objective To identify key proteins associated with sudden cardiac death(SCD)caused by lethal arrhythmia and to explore their potential molecular mechanisms through integrated proteomic analysis,data mining,and bioinformatics.Methods A lethal arrhythmia model was established in 8-week-old male Sprague-Dawley rats,which were divided into an arrhythmia group and a control group.Proteomic techniques were applied to identify and quantify proteins in left ventricular myocardial tissue,and differentially expressed proteins related to arrhythmia were screened.Key proteins were further identified through comparison with target proteins in databases combined with joint analyses.Bioinformatics methods were then used to investigate potential molecular mechanisms.Results A total of 356 differentially expressed proteins were identified,including 189 upregulated and 167 downregulated.Association analysis with target gene proteins identified 71 key proteins,and a protein-protein interaction network was constructed.GO enrichment and KEGG pathway analyses indicated that these key proteins were primarily involved in ion channel dysfunction,enhanced oxidative stress,and autonomic nervous system imbalance.Conclusion This study,through the integration of proteomics,data mining,and bioinformatics,revealed critical molecular mechanisms underlying SCD associated with lethal arrhythmia.These findings provide new perspectives and potential biomarkers for forensic identification and research on the mechanisms of death.
作者
黄阅兵
邱海
陈雯
孟子邻
蔡雨
岳霞
乔东访
Huang Yuebing;Qiu Hai;Chen Wen;Meng Zilin;Cai Yu;Yue Xia;Qiao Dongfang(College of Forensic Medicine,Southern Medical University,Guangzhou,Guangdong,510515)
出处
《中国法医学杂志》
2025年第4期444-449,共6页
Chinese Journal of Forensic Medicine
基金
广东省自然科学基金(2023A1515011601)。