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用于预测多发伤猪模型中器官功能障碍和急性凝血病的潜在生物标志物组合

Potential biomarker panel for predicting organ dysfunction and acute coagulopathy in a polytrauma porcine model.

作者信息

Wong Yong Chiat, Lai Yi Yang, Tan Mui Hong, Tan Chuen Seng, Wu Jian, Zeng Lewis Zheng Jie, Lu Jia, Moochhala Shabbir

机构信息

*Defence Medical and Environmental Research Institute, DSO National Laboratories; and †Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.

出版信息

Shock. 2015 Feb;43(2):157-65. doi: 10.1097/SHK.0000000000000279.

DOI:10.1097/SHK.0000000000000279
PMID:25347751
Abstract

Traumatic injury remains a major cause of morbidity and mortality worldwide, and patients who survived the initial insult are susceptible to an overwhelming inflammatory dysfunction that will lead to acute coagulopathy of trauma (ACOT) and subsequently multiple organ dysfunction syndrome (MODS). Multiple organ dysfunction syndrome-related scoring systems, although they measure organ dysfunction, present clinical markers, and single-cytokine estimates are unable to predict accurately the events of MODS in the clinical setting to aid risk stratification. In this study, a pig model comprising the lethal triad of trauma was used to determine prognostic patterns of early circulating trauma markers so as to predict the development of MODS and ACOT. We measured early expression of several biomarkers (neutrophil gelatinase-associated protein, high-mobility group box 1, C-reactive protein, tumor necrosis factor-α, heart-type fatty acid binding protein, and D-dimers) and clinical parameters for various organ injuries and abnormalities (creatinine, creatine kinase myocardial band, aspartate aminotransferase, and maximum clot firmness) at later time points. The strength of association between the early expression of several biomarkers to the development of MODS and ACOT in polytraumatized pigs was tested using the Spearman correlation coefficient. These biomarkers were found useful to predict the onset of renal, cardiac, hepatic, and hemostatic abnormalities. The findings show that these biomarkers could help to identify, guide, and streamline damage control surgery and earlier intervention to reverse the detrimental outcomes of MODS and ACOT.

摘要

创伤性损伤仍然是全球发病和死亡的主要原因,在初始创伤中存活下来的患者易患严重的炎症功能障碍,这将导致创伤性急性凝血病(ACOT),随后发展为多器官功能障碍综合征(MODS)。多器官功能障碍综合征相关的评分系统,虽然可以测量器官功能障碍、呈现临床标志物,且单一细胞因子评估也无法在临床环境中准确预测MODS的发生以辅助风险分层。在本研究中,使用包含创伤致死三联征的猪模型来确定早期循环创伤标志物的预后模式,从而预测MODS和ACOT的发展。我们测量了几种生物标志物(中性粒细胞明胶酶相关蛋白、高迁移率族蛋白B1、C反应蛋白、肿瘤坏死因子-α、心脏型脂肪酸结合蛋白和D-二聚体)的早期表达,以及在后续时间点各种器官损伤和异常情况(肌酐、肌酸激酶心肌型同工酶、天冬氨酸转氨酶和最大血凝块硬度)的临床参数。使用Spearman相关系数检验了多创伤猪中几种生物标志物的早期表达与MODS和ACOT发展之间的关联强度。发现这些生物标志物有助于预测肾脏、心脏、肝脏和止血异常的发生。研究结果表明,这些生物标志物有助于识别、指导和简化损伤控制手术以及早期干预,以扭转MODS和ACOT的有害后果。

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