The Secretome Deregulations in a Rat Model of Endotoxemic Shock.

The Secretome Deregulations in a Rat Model of Endotoxemic Shock.
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DOI:
10.1155/2021/6650464
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发表时间:
2021
影响因子:
--
通讯作者:
Lauzier B
Lauzier B
中科院分区:
生物学2区
文献类型:
--
作者:
Blangy-Letheule A;Persello A;Michelland S;Cunin V;Souab F;Aillerie V;Dhot J;Erraud A;Montnach J;Seve M;Bourgoin-Voillard S;Rozec B;De Waard M;Lauzier B

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感染性休克是一种与器官衰竭相关的全身性炎症反应综合征。早期临床诊断有利于降低病死率。然而,目前缺乏可预测的生物标志物。分泌体是细胞、组织或生物体在特定时间和特定条件下分泌的一组蛋白质。血浆分泌组很容易从生物液中获得,这是发现新的生物标记物的好机会,这些标记物可以用非靶向的“基因组”策略进行研究。目的:鉴定大鼠内毒素休克模型分泌组中的相关去调节蛋白(DEP)。大鼠静脉注射脂多糖(内毒素,伤寒沙门氏菌,0.5 mg/kg)诱导内毒素性休克,并与对照组(乳酸林格液,iv)比较。在异氟醚麻醉下,颈动脉插管监测平均动脉压(MAP)和心率(HR),并在不同时间点(T0和T50或T0和T90,使用EDTA和蛋白水解酶抑制剂)采血。样品准备用于基于无标记定量的大规模串联质谱仪(MS-MS),以允许识别内毒素血症条件下解除管制的蛋白质。基因本体论(GO)分析定义了DEP参与的几个生物过程(BP)簇。休克诱导90分钟后,与对照组相比,内毒素组的MAP下降(-45%,p<0.05),乳酸水平升高(+27.5%,p<0.05)。蛋白质组学分析显示,内毒素组在注射后50分钟和90分钟分别有10和33个DEP。在这些时间点,GO-BP显示参与氧化应激反应和凝血反应的途径发生了变化。这项研究提出了一种在败血症休克中识别相关DEP的方法,并为理解脓毒症时分泌体的适应提供了新的见解。
Septic shock is a systemic inflammatory response syndrome associated with organ failures. Earlier clinical diagnosis would be of benefit to a decrease in the mortality rate. However, there is currently a lack of predictive biomarkers. The secretome is the set of proteins secreted by a cell, tissue, or organism at a given time and under certain conditions. The plasma secretome is easily accessible from biological fluids and represents a good opportunity to discover new biomarkers that can be studied with nontargeted “omic” strategies. To identify relevant deregulated proteins (DEP) in the secretome of a rat endotoxemic shock model. Endotoxemic shock was induced in rats by intravenous injection of lipopolysaccharides (LPS, S. enterica typhi, 0.5 mg/kg) and compared to controls (Ringer Lactate, iv). Under isoflurane anesthesia, carotid cannulation allowed mean arterial blood pressure (MAP) and heart rate (HR) monitoring and blood sampling at different time points (T0 and T50 or T0 and T90, with EDTA and protease inhibitor). Samples were prepared for large-scale tandem mass spectrometry (MS-MS) based on a label-free quantification to allow identification of the proteins deregulated upon endotoxemic conditions. A Gene Ontology (GO) analysis defined several clusters of biological processes (BP) in which the DEP are involved. Ninety minutes after shock induction, the LPS group presents a reduction in MAP (-45%, p < 0.05) and increased lactate levels (+27.5%, p < 0.05) compared to the control group. Proteomic analyses revealed 10 and 33 DEP in the LPS group, respectively, at 50 and 90 minutes after LPS injection. At these time points, GO-BP showed alterations in pathways involved in oxidative stress response and coagulation. This study proposes an approach to identify relevant DEP in septic shock and brings new insights into the understanding of the secretome adaptations upon sepsis.
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