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组织损伤和出血性休克的组学特征在猪。

Omics Signatures of Tissue Injury and Hemorrhagic Shock in Swine.

机构信息

Department of Biochemistry and Molecular Genetics, University of Colorado Denver-Anschutz Medical Campus, Aurora, CO.

Department of Surgery, University of Colorado-Anschutz Medical Campus, Aurora, CO.

出版信息

Ann Surg. 2023 Dec 1;278(6):e1299-e1312. doi: 10.1097/SLA.0000000000005944. Epub 2023 Jun 19.

DOI:10.1097/SLA.0000000000005944
PMID:37334680
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10728352/
Abstract

OBJECTIVE

Advanced mass spectrometry methods were leveraged to analyze both proteomics and metabolomics signatures in plasma upon controlled tissue injury (TI) and hemorrhagic shock (HS)-isolated or combined-in a swine model, followed by correlation to viscoelastic measurements of coagulopathy via thrombelastography.

BACKGROUND

TI and HS cause distinct molecular changes in plasma in both animal models and trauma patients. However, the contribution to coagulopathy of trauma, the leading cause of preventable mortality in this patient population remains unclear. The recent development of a swine model for isolated or combined TI+HS facilitated the current study.

METHODS

Male swine (n=17) were randomized to either isolated or combined TI and HS. Coagulation status was analyzed by thrombelastography during the monitored time course. The plasma fractions of the blood draws (at baseline; end of shock; and at 30 minutes, 1, 2, and 4 hours after shock) were analyzed by mass spectrometry-based proteomics and metabolomics workflows.

RESULTS

HS-isolated or combined with TI-caused the most severe omic alterations during the monitored time course. While isolated TI delayed the activation of coagulation cascades. Correlation to thrombelastography parameters of clot strength (maximum amplitude) and breakdown (LY30) revealed signatures of coagulopathy which were supported by analysis of gene ontology-enriched biological pathways.

CONCLUSION

The current study provides a comprehensive characterization of proteomic and metabolomic alterations to combined or isolated TI and HS in a swine model and identifies early and late omics correlates to viscoelastic measurements in this system.

摘要

目的

利用先进的质谱方法分析受控组织损伤(TI)和失血性休克(HS)单独或联合作用于猪模型后的蛋白质组学和代谢组学特征,然后通过血栓弹性描记术与凝血功能的粘弹性测量相关联。

背景

TI 和 HS 在动物模型和创伤患者的血浆中引起不同的分子变化。然而,创伤导致的凝血功能障碍对该患者群体中导致可预防死亡率的主要原因的贡献尚不清楚。最近开发的单独或联合 TI+HS 的猪模型促成了本研究。

方法

雄性猪(n=17)随机分为单独或联合 TI 和 HS 组。在监测的时间过程中通过血栓弹性描记术分析凝血状态。在采血的血浆部分(基线;休克结束时;休克后 30 分钟、1 小时、2 小时和 4 小时)通过基于质谱的蛋白质组学和代谢组学工作流程进行分析。

结果

HS 单独或与 TI 联合导致监测时间过程中最严重的组学改变。而单独的 TI 延迟了凝血级联的激活。与血栓弹性图参数(最大振幅)和分解(LY30)的相关性显示了凝血功能障碍的特征,这些特征得到了对富集生物学途径的基因本体分析的支持。

结论

本研究提供了一个综合的猪模型中 TI 和 HS 单独或联合的蛋白质组学和代谢组学改变的描述,并确定了早期和晚期组学与该系统粘弹性测量的相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d15/10728352/a260bab8494b/nihms-1907428-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d15/10728352/61b90816be28/nihms-1907428-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d15/10728352/c6a5462888e3/nihms-1907428-f0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d15/10728352/d75a516cd74b/nihms-1907428-f0004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d15/10728352/c5d148483703/nihms-1907428-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d15/10728352/a260bab8494b/nihms-1907428-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d15/10728352/61b90816be28/nihms-1907428-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d15/10728352/c6a5462888e3/nihms-1907428-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d15/10728352/a170c39308cf/nihms-1907428-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d15/10728352/d75a516cd74b/nihms-1907428-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d15/10728352/95e08df15037/nihms-1907428-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d15/10728352/c5d148483703/nihms-1907428-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d15/10728352/a260bab8494b/nihms-1907428-f0007.jpg

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