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急性高凝状态大鼠模型尿液生物标志物的蛋白质组学分析

Proteome Analysis of Urinary Biomarkers in Acute Hypercoagulable State Rat Model.

作者信息

Jing Jian, Du Zhenhuan, Qin Weiwei

机构信息

Beijing Key Lab of Genetic Engineering and Biotechnology, College of Life Sciences, Beijing Normal University, Beijing, China.

出版信息

Front Mol Biosci. 2021 Apr 30;8:634606. doi: 10.3389/fmolb.2021.634606. eCollection 2021.

DOI:10.3389/fmolb.2021.634606
PMID:33996895
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8119894/
Abstract

Thrombotic diseases are usually preceded by a hypercoagulable state in the body. This study aimed to screen potential urinary biomarkers for hypercoagulable state based on proteome analysis. Wistar rats were administered with the hemostatic agent etamsylate to establish hypercoagulable state. Urine samples were collected for proteome analysis. We found 20 proteins with levels more than 1.5-fold in difference between control rats and model rats. We searched human homologs of 20 rat proteins and identified 13 human proteins. Of the 13 human homologous proteins, nine were members of human core urinary proteome. Human homologous proteins of differential proteins were highly expressed in 31 human tissues, especially in the kidneys followed by digestive system and reproductive system. Surprisingly, we did not identify known coagulation factors as differential proteins in the urine of model rats. Hypercoagulable state of the body may not involve direct changes in coagulation factors but causes the changes upstream of the coagulation cascade system. Common differential urinary proteins between different hypercoagulable states suggest some common pathways in the formation of hypercoagulable states and may serve as potential biomarkers for the prevention and treatment of thrombotic diseases.

摘要

血栓性疾病通常在身体处于高凝状态之前出现。本研究旨在基于蛋白质组分析筛选高凝状态的潜在尿液生物标志物。给Wistar大鼠施用止血剂酚磺乙胺以建立高凝状态。收集尿液样本进行蛋白质组分析。我们发现20种蛋白质在对照大鼠和模型大鼠之间的水平差异超过1.5倍。我们搜索了20种大鼠蛋白质的人类同源物,并鉴定出13种人类蛋白质。在这13种人类同源蛋白质中,有9种是人类核心尿液蛋白质组的成员。差异蛋白质的人类同源蛋白质在31种人类组织中高表达,尤其是在肾脏中,其次是消化系统和生殖系统。令人惊讶的是,我们在模型大鼠尿液中未将已知凝血因子鉴定为差异蛋白质。身体的高凝状态可能不涉及凝血因子的直接变化,而是导致凝血级联系统上游的变化。不同高凝状态之间常见的差异尿液蛋白质提示了高凝状态形成中的一些共同途径,并且可能作为血栓性疾病预防和治疗的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804b/8119894/d18840e0afa7/fmolb-08-634606-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804b/8119894/ddbd94541d4e/fmolb-08-634606-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804b/8119894/91a9e6de828c/fmolb-08-634606-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804b/8119894/31c5c62f4683/fmolb-08-634606-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804b/8119894/32163e952f3c/fmolb-08-634606-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804b/8119894/e8a59ba6526b/fmolb-08-634606-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804b/8119894/d18840e0afa7/fmolb-08-634606-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804b/8119894/ddbd94541d4e/fmolb-08-634606-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804b/8119894/91a9e6de828c/fmolb-08-634606-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804b/8119894/31c5c62f4683/fmolb-08-634606-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804b/8119894/32163e952f3c/fmolb-08-634606-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804b/8119894/e8a59ba6526b/fmolb-08-634606-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/804b/8119894/d18840e0afa7/fmolb-08-634606-g006.jpg

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本文引用的文献

1
Dynamic changes of urinary proteins in a rat model of acute hypercoagulable state induced by tranexamic acid.氨甲环酸诱导急性高凝状态大鼠模型尿液蛋白的动态变化。
J Cell Physiol. 2019 Jul;234(7):10809-10818. doi: 10.1002/jcp.27904. Epub 2018 Dec 7.
2
Urinary proteome analysis of acute hypercoagulable state in rat model induced by ε-aminocaproic acid.尿蛋白质组分析在 ε-氨基己酸诱导的大鼠急性高凝状态模型中的应用。
Biomed Pharmacother. 2019 Feb;110:275-284. doi: 10.1016/j.biopha.2018.11.148. Epub 2018 Dec 2.
3
Urine biomarkers in the early stages of diseases: current status and perspective.
疾病早期阶段的尿液生物标志物:现状与展望
Discov Med. 2018 Feb;25(136):57-65.
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Predictive Factors for Complete Response and Recurrence after Transarterial Chemoembolization in Hepatocellular Carcinoma.肝细胞癌经动脉化疗栓塞术后完全缓解和复发的预测因素
Gut Liver. 2017 May 15;11(3):409-416. doi: 10.5009/gnl16001.
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The Laboratory Diagnosis of the Antiphospholipid Syndrome.抗磷脂综合征的实验室诊断
Indian J Hematol Blood Transfus. 2017 Mar;33(1):8-14. doi: 10.1007/s12288-016-0739-y. Epub 2016 Oct 22.
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Glypican-3 and KRT19 are markers associating with metastasis and poor prognosis of pancreatic ductal adenocarcinoma.磷脂酰肌醇蛋白聚糖-3和细胞角蛋白19是与胰腺导管腺癌转移及预后不良相关的标志物。
Cancer Biomark. 2016;17(4):397-404. doi: 10.3233/CBM-160655.
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Adipokine zinc-alpha-2-glycoprotein as a novel urinary biomarker presents earlier than microalbuminuria in diabetic nephropathy.脂肪因子锌-α-2-糖蛋白作为一种新型尿液生物标志物,在糖尿病肾病中比微量白蛋白尿出现得更早。
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