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实验性呼吸机诱导的肺损伤猪模型中的细胞外囊泡释放

Extracellular vesicle release in an experimental ventilator-induced lung injury porcine model.

作者信息

Larsson Niklas, Claesson Jonas, Lehtipalo Stefan, Behndig Annelie, Mobarrez Fariborz, Haney Michael

机构信息

Department of Diagnostics and Intervention, Anesthesiology and Intensive Care Medicine, Umeå University, Umeå, Sweden.

Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.

出版信息

PLoS One. 2025 Apr 9;20(4):e0320144. doi: 10.1371/journal.pone.0320144. eCollection 2025.

DOI:10.1371/journal.pone.0320144
PMID:40202940
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11981186/
Abstract

Harmful effects of mechanical ventilation with large tidal volumes, volutrauma, may contribute much to diffuse acute lung injury. Extracellular vesicles have been noted in the context of vital organ injury. We hypothesized that extracellular vesicles from acutely injured lung can be found in both lung and blood. In a two-hit experimental porcine model, we tested if extracellular vesicles could be detected in bronchoalveolar lavage fluid and in plasma over a six-hour period of large tidal volume ventilation after surfactant depletion. After 2 hours of volutrauma, bronchoalveolar lavage fluid showed increased levels of extracellular vesicles containing nucleic acids (stained by SYTO 13) and those positive for both SYTO 13 and HMGB1. No such increase was detected in plasma at any timepoint during the six-hour experiments. This shows that nucleic acid-containing extracellular vesicles appear to be involved in progression of lung injury, possibly indicating cellular damage, but their potential to serve as diagnostic biomarkers of acute lung injury progression, based on plasma sampling, and in the very early phase, is not confirmed by these findings.

摘要

大潮气量机械通气的有害影响,即容积伤,可能在弥漫性急性肺损伤中起很大作用。在重要器官损伤的情况下已发现细胞外囊泡。我们假设在急性损伤的肺中发现的细胞外囊泡可在肺和血液中均被检测到。在一个双打击实验性猪模型中,我们测试了在表面活性剂耗竭后的大潮气量通气6小时期间,支气管肺泡灌洗液和血浆中是否能检测到细胞外囊泡。在容积伤2小时后,支气管肺泡灌洗液中含有核酸的细胞外囊泡(用SYTO 13染色)以及对SYTO 13和HMGB1均呈阳性的细胞外囊泡水平升高。在6小时实验期间的任何时间点,血浆中均未检测到这种升高。这表明含核酸的细胞外囊泡似乎参与了肺损伤的进展,可能表明细胞损伤,但基于血浆采样,这些发现并未证实它们在急性肺损伤进展的极早期作为诊断生物标志物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11981186/f49462303527/pone.0320144.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11981186/8c561f712e15/pone.0320144.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11981186/adbc2221c570/pone.0320144.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11981186/413d66768394/pone.0320144.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11981186/f49462303527/pone.0320144.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11981186/8c561f712e15/pone.0320144.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11981186/adbc2221c570/pone.0320144.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11981186/413d66768394/pone.0320144.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/721c/11981186/f49462303527/pone.0320144.g004.jpg

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Lab Chip. 2024 Sep 10;24(18):4390-4402. doi: 10.1039/d4lc00143e.
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A beginner's guide to study extracellular vesicles in human blood plasma and serum.人类血浆和血清中外泌体研究入门指南。
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A heterogenous population of extracellular vesicles mobilize to the alveoli postinjury.损伤后,异质细胞外囊泡群迁移到肺泡。
J Trauma Acute Care Surg. 2024 Mar 1;96(3):371-377. doi: 10.1097/TA.0000000000004176. Epub 2023 Nov 26.
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Plasma and bronchoalveolar lavage fluid oxylipin levels in experimental porcine lung injury.实验性猪肺损伤中血浆和支气管肺泡灌洗液氧化应激产物水平。
Prostaglandins Other Lipid Mediat. 2022 Jun;160:106636. doi: 10.1016/j.prostaglandins.2022.106636. Epub 2022 Mar 17.
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CD14-positive extracellular vesicles in bronchoalveolar lavage fluid as a new biomarker of acute respiratory distress syndrome.支气管肺泡灌洗液中 CD14 阳性细胞外囊泡作为急性呼吸窘迫综合征的一种新生物标志物。
Am J Physiol Lung Cell Mol Physiol. 2022 Apr 1;322(4):L617-L624. doi: 10.1152/ajplung.00052.2022. Epub 2022 Mar 2.
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