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S100A8 作为急性深静脉血栓诊断标志物的初步临床分析及通路研究。

Preliminary clinical analysis and pathway study of S100A8 as a biomarker for the diagnosis of acute deep vein thrombosis.

机构信息

Graduate School, Hebei North University, Zhangjiakou, 075000, Hebei, China.

Vascular Gland Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei, China.

出版信息

Sci Rep. 2024 Jun 10;14(1):13298. doi: 10.1038/s41598-024-61728-6.

DOI:10.1038/s41598-024-61728-6
PMID:38858401
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11164926/
Abstract

Herein, we aimed to identify blood biomarkers that compensate for the poor specificity of D-dimer in the diagnosis of deep vein thrombosis (DVT). S100A8 was identified by conducting protein microarray analysis of blood samples from patients with and without DVT. We used ELISA to detect S100A8, VCAM-1, and ICAM-1 expression levels in human blood and evaluated their correlations. Additionally, we employed human recombinant protein S100A8 to induce human umbilical vein endothelial cells and examined the role of the TLR4/MAPK/VCAM-1 and ICAM-1 signaling axes in the pathogenic mechanism of S100A8. Simultaneously, we constructed a rat model of thrombosis induced by inferior vena cava stenosis and detected levels of S100A8, VCAM-1, and ICAM-1 in the blood of DVT rats using ELISA. The associations of thrombus tissue, neutrophils, and CD68-positive cells with S100A8 and p38MAPK, TLR4, and VCAM-1 expression levels in vein walls were explored. The results revealed that blood S100A8 was significantly upregulated during the acute phase of DVT and activated p38MAPK expression by combining with TLR4 to enhance the expression and secretion of VCAM-1 and ICAM-1, thereby affecting the occurrence and development of DVT. Therefore, S100A8 could be a potential biomarker for early diagnosis and screening of DVT.

摘要

在此,我们旨在确定可弥补 D-二聚体在深静脉血栓(DVT)诊断中特异性不足的血液生物标志物。通过对 DVT 患者和无 DVT 患者的血液样本进行蛋白质微阵列分析,鉴定出 S100A8。我们使用 ELISA 检测人血中 S100A8、VCAM-1 和 ICAM-1 的表达水平,并评估它们之间的相关性。此外,我们使用人重组蛋白 S100A8 诱导人脐静脉内皮细胞,并研究 TLR4/MAPK/VCAM-1 和 ICAM-1 信号通路在 S100A8 致病机制中的作用。同时,我们构建了下腔静脉狭窄诱导的大鼠血栓模型,并用 ELISA 检测 DVT 大鼠血液中 S100A8、VCAM-1 和 ICAM-1 的水平。探讨血栓组织、中性粒细胞和 CD68 阳性细胞与 S100A8 和 p38MAPK、TLR4 和 VCAM-1 表达水平在静脉壁中的相关性。结果表明,在 DVT 的急性期,血液 S100A8 明显上调,并与 TLR4 结合激活 p38MAPK 的表达,增强 VCAM-1 和 ICAM-1 的表达和分泌,从而影响 DVT 的发生和发展。因此,S100A8 可能是 DVT 早期诊断和筛查的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c598/11164926/f3639bd4b0de/41598_2024_61728_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c598/11164926/d2e0fb9b01f1/41598_2024_61728_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c598/11164926/f3639bd4b0de/41598_2024_61728_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c598/11164926/d2e0fb9b01f1/41598_2024_61728_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c598/11164926/f3639bd4b0de/41598_2024_61728_Fig3_HTML.jpg

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