Huang Yuebing, Qiu Hai, Chen Qianling, Meng Zilin, Qiao Dongfang, Yue Xia
Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China.
Int J Mol Sci. 2024 Nov 26;25(23):12710. doi: 10.3390/ijms252312710.
Mechanical asphyxia presents a challenging diagnostic issue in forensic medicine due to its often covert nature, and the signs visible during an autopsy are usually not specific. Despite some progress in understanding hypoxia's effects, traditional methods' inherent limitations might overlook new biomarkers in mechanical asphyxia. This study employed 4D-DIA proteomics to explore the protein expression profiles of cardiac samples under conditions of mechanical asphyxia. Proteomic analysis identified 271 and 371 differentially expressed proteins in the strangulation and suffocation groups, respectively, compared to the control group. Seventy-eight differentially expressed proteins were identified across different mechanical asphyxia groups compared to the control group. GO and KEGG analysis showed enrichment in pathways, including complement and coagulation cascades, cAMP and cGMP-PKG signaling pathways, inflammatory mediator regulation of TRP channels, and phagosomes. Through stringent selection based on protein interactions, ALKBH5, NAA10, and CLPB were identified as potential diagnostic biomarkers. ALKBH5 showed increased expression in asphyxia models, while NAA10 and CLPB were downregulated; these biomarker changes were validated in both animal models and human cardiac samples. This study highlights the potential of proteomics in discovering reliable biomarkers, which can enhance the specificity of mechanical asphyxia diagnosis in forensic practice, provide new insights into the pathophysiological mechanisms of mechanical asphyxia, and offer new perspectives for diagnosing mechanical asphyxia.
由于机械性窒息通常具有隐匿性，在法医学中它是一个具有挑战性的诊断问题，并且尸检时可见的体征通常不具有特异性。尽管在理解缺氧的影响方面取得了一些进展，但传统方法的固有局限性可能会忽略机械性窒息中的新生物标志物。本研究采用4D-DIA蛋白质组学来探索机械性窒息条件下心脏样本的蛋白质表达谱。蛋白质组学分析确定，与对照组相比，绞窄组和窒息组分别有271种和371种差异表达蛋白质。与对照组相比，在不同机械性窒息组中鉴定出78种差异表达蛋白质。GO和KEGG分析表明，这些差异表达蛋白质在补体和凝血级联、cAMP和cGMP-PKG信号通路、TRP通道的炎症介质调节以及吞噬体等通路中富集。通过基于蛋白质相互作用的严格筛选，确定ALKBH5、NAA10和CLPB为潜在的诊断生物标志物。ALKBH5在窒息模型中表达增加，而NAA10和CLPB表达下调；这些生物标志物的变化在动物模型和人类心脏样本中均得到验证。本研究突出了蛋白质组学在发现可靠生物标志物方面的潜力，这可以提高法医学实践中机械性窒息诊断的特异性，为机械性窒息的病理生理机制提供新的见解，并为机械性窒息的诊断提供新的视角。
