在失血性休克患者中，内皮细胞功能障碍的生物标志物在复苏后仍然存在。

Biomarkers of endothelial cell dysfunction persist beyond resuscitation in patients with hemorrhagic shock.

机构信息

From the Department of Surgery (A.Z.), Shock Trauma and Anesthesiology Research Organized Research Center, Baltimore, Maryland; Shock Trauma and Anesthesiology Research Organized Research Center (A.Z., F.W., W.C., L.Z., R.V., H.H., R.A.K.), Department of Anesthesia (W.C., L.Z., H.H.), and Department of Surgery (A.M.C.), University of Maryland School of Medicine, Baltimore, Maryland; Bloodworks Research Institute (J.F.D.); Hematology Division, Department of Medicine (J.F.D.), University of Washington School of Medicine, Seattle, Washington; Department of Laboratory Medicine (S.P.), Department of Surgery, University of California, San Francisco, San Francisco, California; and Shock Trauma Center (R.A.K.), University of Maryland School of Medicine, Baltimore, Maryland.

出版信息

J Trauma Acute Care Surg. 2022 Nov 1;93(5):572-578. doi: 10.1097/TA.0000000000003758. Epub 2022 Aug 5.

DOI:10.1097/TA.0000000000003758

PMID:35939376

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9613546/

Abstract

BACKGROUND

It has been shown that microRNA-19b (miR-19b) binds to and degrades syndecan-1 after hemorrhagic shock (HS) and contributes to endothelial dysfunction in vitro and in vivo. The objective of the current study was to assess longitudinal changes in miR-19b and syndecan-1 in HS patients.

METHODS

Blood samples from HS patients (blood pressure <90 mm Hg and ≥2 U blood) were collected upon admission, completion of hemostasis, and after 24 hours for miR-19b (quantitative reverse transcription PCR) and syndecan-1 (enzyme-linked immunosorbent assay) and compared with controls and minimally injured (Injury Severity Score, ≤9). Inflammatory cytokines were measured (Luminex [Thermo Fisher, Waltham, MA]). Correlations between syndecan-1, miR-19b, inflammatory markers, and patient outcomes were performed. Logistic regression models were developed for outcomes.

RESULTS

Thirty-four HS patients were studied: age, 46 (19-89) years; male, 82%; penetrating, 35%; Injury Severity Score, 24 ± 10; and blood products at 24 hours, 21 ± 19 U. MicroRNA-19b was increased upon arrival and further increased over time: 4.6 → 6.7 → 24.1-fold change compared with 0.1 and 1.2 for minimally injured patients and controls, respectively. Syndecan-1 was increased to 42.6 → 50 → 51.5 ng/mL over time compared with 14.7 and 23.5 for minimally injured and controls, respectively. Values for both biomarkers remained significantly increased through 24 hours and were associated with a persistent increase in inflammatory cytokines. Admission syndecan-1 significantly predicted mortality, coagulopathy, and massive transfusion.

CONCLUSION

We have shown for the first time that miR-19b and syndecan-1 were biomarkers for endothelial dysfunction independent of resuscitation. MicroRNA-19b did not demonstrate a strong correlation with syndecan-1 nor outcomes. Admission syndecan-1, however, remains a strong prognostic marker, but its elevation over time suggests a versatile role following HS that requires further investigation.

LEVEL OF EVIDENCE

Prognostic/Epidemiological; Level II.

摘要

背景

已经表明，微小 RNA-19b（miR-19b）在出血性休克（HS）后与硫酸乙酰肝素蛋白聚糖-1（syndecan-1）结合并使其降解，这有助于体外和体内的血管内皮功能障碍。本研究的目的是评估 HS 患者 miR-19b 和 syndecan-1 的纵向变化。

方法

在入院时、止血完成时和 24 小时后，采集 HS 患者（血压<90mmHg 和≥2U 血）的血液样本，用于 miR-19b（定量逆转录 PCR）和 syndecan-1（酶联免疫吸附试验）的检测，并与对照组和最小损伤（损伤严重程度评分，≤9）患者进行比较。采用 Luminex（Thermo Fisher，Waltham，MA）测量炎症细胞因子。进行 syndecan-1、miR-19b、炎症标志物与患者结局之间的相关性分析。为结局建立逻辑回归模型。

结果

共研究了 34 名 HS 患者：年龄 46（19-89）岁；男性占 82%；穿透伤占 35%；损伤严重程度评分 24±10；24 小时用血制品 21±19U。miR-19b 在入院时增加，并随时间进一步增加：与最小损伤患者和对照组的 0.1 和 1.2 相比，分别为 4.6→6.7→24.1 倍。syndecan-1 随时间增加至 42.6→50→51.5ng/mL，与最小损伤和对照组的 14.7 和 23.5 相比。这两种生物标志物的数值在 24 小时内仍显著升高，并与炎症细胞因子的持续增加相关。入院时 syndecan-1 显著预测死亡率、凝血障碍和大量输血。

结论

我们首次表明，miR-19b 和 syndecan-1 是独立于复苏的血管内皮功能障碍的生物标志物。miR-19b 与 syndecan-1 或结局之间没有很强的相关性。然而，入院时 syndecan-1 仍然是一个强有力的预后标志物，但随着时间的推移其升高表明其在 HS 后具有广泛的作用，需要进一步研究。