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创伤患者血清中基质金属蛋白酶 1、2、7 及其组织抑制剂 1、2、3、4 的水平:时间轨迹、相关性及其对死亡率的预测能力。

Serum levels of matrix metalloproteinases 1, 2, and 7, and their tissue inhibitors 1, 2, 3, and 4 in polytraumatized patients: Time trajectories, correlations, and their ability to predict mortality.

机构信息

University Department of Orthopedics and Trauma Surgery, Medical University of Vienna, Vienna, Austria.

University Department of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.

出版信息

PLoS One. 2024 Mar 8;19(3):e0300258. doi: 10.1371/journal.pone.0300258. eCollection 2024.

Abstract

There has been limited research on assessing metalloproteinases (MMPs) 1, 2, and 7, as well as their tissue inhibitors (TIMPs) 1, 2, 3, and 4 in the context of polytrauma. These proteins play crucial roles in various physiological and pathological processes and could be a reliable tool in polytrauma care. We aimed to determine their clinical relevance. We assessed 24 blunt polytrauma survivors and 12 fatalities (mean age, 44.2 years, mean ISS, 45) who were directly admitted to our Level I trauma center and spent at least one night in the intensive care unit. We measured serum levels of the selected proteins on admission (day 0) and days 1, 3, 5, 7, and 10. The serum levels of the seven proteins varied considerably among individuals, resulting in similar median trend curves for TIMP1 and TIMP4 and for MMP1, MMP2, TIMP2, and TIMP3. We also found a significant interrelationship between the MMP2, TIMP2, and TIMP3 levels at the same measurement points. Furthermore, we calculated significant cross-correlations between MMP7 and MMP1, TIMP1 and MMP7, TIMP3 and MMP1, TIMP3 and MMP2, and TIMP4 and TIMP3 and an almost significant correlation between MMP7 and TIMP1 for a two-day-lag. The autocorrelation coefficient reached statistical significance for MMP1 and TIMP3. Finally, lower TIMP1 serum levels were associated with in-hospital mortality upon admission. The causal effects and interrelationships between selected proteins might provide new insights into the interactions of MMPs and TIMPs. Identifying the underlying causes might help develop personalized therapies for patients with multiple injuries. Administering recombinant TIMP1 or increasing endogenous production could improve outcomes for those with multiple injuries. However, before justifying further investigations into basic research and clinical relevance, our findings must be validated in a multicenter study using independent cohorts to account for clinical and biological variability.

摘要

在多发伤的背景下,关于金属蛋白酶(MMPs)1、2 和 7 及其组织抑制剂(TIMPs)1、2、3 和 4 的评估研究有限。这些蛋白质在各种生理和病理过程中发挥着重要作用,可能是多发伤护理的可靠工具。我们旨在确定它们的临床相关性。我们评估了 24 名钝器多发伤幸存者和 12 名死亡患者(平均年龄 44.2 岁,ISS 平均 45),他们直接被收入我院 1 级创伤中心,并在重症监护病房至少度过了一个晚上。我们在入院时(第 0 天)以及第 1、3、5、7 和 10 天测量了选定蛋白质的血清水平。七种蛋白质的血清水平在个体之间差异很大,导致 TIMP1 和 TIMP4 以及 MMP1、MMP2、TIMP2 和 TIMP3 的中位数趋势曲线相似。我们还发现同一测量点 MMP2、TIMP2 和 TIMP3 水平之间存在显著的相互关系。此外,我们计算了 MMP7 和 MMP1、TIMP1 和 MMP7、TIMP3 和 MMP1、TIMP3 和 MMP2 以及 TIMP4 和 TIMP3 之间的显著交叉相关性,并且 MMP7 和 TIMP1 之间存在几乎显著的相关性。两个滞后日。MMP1 和 TIMP3 的自相关系数达到统计学意义。最后,入院时 TIMP1 血清水平较低与院内死亡率相关。选定蛋白质之间的因果效应和相互关系可能为 MMPs 和 TIMPs 的相互作用提供新的见解。确定潜在原因可能有助于为多发性损伤患者开发个性化治疗方法。给予重组 TIMP1 或增加内源性产生可能会改善多发性损伤患者的预后。但是,在为基础研究和临床相关性进行进一步调查之前,我们的发现必须在使用独立队列的多中心研究中得到验证,以解释临床和生物学变异性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3749/10923431/2eb77f8eb4df/pone.0300258.g001.jpg

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