Cao Yang, Li Jiaxin, Cai Minghui, Qiang Na, Wang Jiao, Gao Qiang, Zhang Zhitao, Xu Jie, Zhu Hui
School of Basic Medical Sciences, Harbin Medical University, Harbin, China.
School of Basic Medical Sciences, Harbin Medical University, Harbin, China; Key Laboratory of Preservation of Human Genetic Resources and Disease Control in China (Harbin Medical University), Ministry of Education, Harbin, China.
Biochem Biophys Res Commun. 2025 Aug 15;775:152116. doi: 10.1016/j.bbrc.2025.152116. Epub 2025 May 29.
This study used DIA mass spectrometry to identify novel plasma protein biomarkers for sepsis, aiming to find new diagnostic targets.
A sepsis model in C57BL/6 mice, divided into Control and LPS groups, assessed survival post-LPS. Plasma samples measured inflammatory (IL-1β, IL-6, TNF-α) and thrombi (sTM, D2D) markers via ELISA. Organ changes in lungs, liver, kidneys, heart, and spleen were evaluated via HE staining. DIA proteomics identified proteins, and ROC curve validation assessed the predictive value of combined protein detection for sepsis diagnosis.
Survival rates showed about 50 % mortality in the LPS group 8-10 h post-administration, with all mice dying within 14 h. ELISA results showed higher levels of inflammatory and thrombotic markers in the LPS group. HE staining revealed organ damage and morphological changes in the LPS group. DIA quantitative proteomics identified 194 differentially expressed proteins (172 upregulated, 22 downregulated). GO terms included chemokine-mediated signaling and cellular response to interleukin-1. KEGG pathways showed enrichment in endocytosis and cytokine interactions. PPI network analysis and hub gene screening revealed key hub genes: IFNG, IL-6, IL-1β, and TIMP1. The ROC curves shows that compared to monitoring a single plasma protein indicator, the combined detection of these proteins are highly predictive for diagnosing sepsis.
IFNG, IL-6, IL-1β and TIMP1 hold potential as novel plasma biomarkers for the combined detection in sepsis patients. This study provides new insights into the diagnosis of plasma biomarkers for sepsis, although further research is needed to assess their functional significance and clinical applications.
本研究采用数据独立采集质谱法鉴定脓毒症新的血浆蛋白生物标志物，旨在寻找新的诊断靶点。
建立C57BL/6小鼠脓毒症模型，分为对照组和脂多糖（LPS）组，评估LPS注射后的生存率。通过酶联免疫吸附测定法（ELISA）检测血浆样本中的炎症标志物（白细胞介素-1β、白细胞介素-6、肿瘤坏死因子-α）和血栓标志物（可溶性血栓调节蛋白、D-二聚体）。通过苏木精-伊红（HE）染色评估肺、肝、肾、心和脾的器官变化。数据独立采集蛋白质组学鉴定蛋白质，通过受试者工作特征（ROC）曲线验证评估联合蛋白质检测对脓毒症诊断的预测价值。
生存率显示，LPS组给药后8 - 10小时死亡率约为50%，所有小鼠在14小时内死亡。ELISA结果显示LPS组炎症和血栓标志物水平较高。HE染色显示LPS组存在器官损伤和形态学变化。数据独立采集定量蛋白质组学鉴定出194种差异表达蛋白（172种上调，22种下调）。基因本体（GO）术语包括趋化因子介导的信号传导和细胞对白细胞介素-1的反应。京都基因与基因组百科全书（KEGG）通路显示在内吞作用和细胞因子相互作用方面富集。蛋白质-蛋白质相互作用（PPI）网络分析和枢纽基因筛选揭示了关键枢纽基因：干扰素-γ（IFNG）、白细胞介素-6、白细胞介素-1β和金属蛋白酶组织抑制因子1（TIMP1）。ROC曲线显示，与监测单一血浆蛋白指标相比，这些蛋白质的联合检测对脓毒症诊断具有高度预测性。
IFNG、白细胞介素-6、白细胞介素-1β和TIMP1有望作为脓毒症患者联合检测的新型血浆生物标志物。本研究为脓毒症血浆生物标志物的诊断提供了新的见解，尽管需要进一步研究来评估它们的功能意义和临床应用。
