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大鼠模型中的呼吸机诱导性肺损伤:它们在这场竞赛中都一样吗?

Ventilator-induced lung injury in rat models: are they all equal in the race?

作者信息

Joelsson Jon Petur, Karason Sigurbergur

机构信息

University of Iceland, Reykjavik, Iceland.

Landspitali-University Hospital, Reykjavik, Iceland.

出版信息

Lab Anim Res. 2025 May 19;41(1):14. doi: 10.1186/s42826-025-00240-y.

DOI:10.1186/s42826-025-00240-y
PMID:40390135
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12090643/
Abstract

Risk of ventilator-induced lung injury (VILI) is an inevitable and precarious accompaniment of ventilator treatment in critically ill patients worldwide. It can both instigate and aggravate acute respiratory distress syndrome (ARDS) where the only prevention or treatment so far has been empirical approach of what is considered to be lung protective ventilator settings in an attempt to shield the lung tissues against the mechanical stress that unavoidably follows ventilator treatment. The weakened state of the patients limits clinical drug research and pushes for drug discovery in animal models. Mice and rats are often the choice of small animal model, representing about 95% of all laboratory animal studies, as their physiology can mimic that which is found in humans. Mice have been a more popular choice for ventilator studies but due to technical issues, there is some advantage gained in using rats as they are substantially larger. Inducing VILI and ARDS in these models can prove challenging and often the acute nature of the injury used to produce similar tissue damage as in humans does not necessarily fully reflect clinical reality. The aim of this review was to analyse and summarize methods of recent publications in the field, describing what approaches have been utilized to simulate these conditions, possibly identifying a common track enabling comparison of results between studies. However, the study shows a high variety of methods employed by researchers causing comparisons of results difficult and perhaps implying that a more standardized approach should be used.

摘要

在全球范围内,机械通气所致肺损伤(VILI)的风险是重症患者机械通气治疗不可避免且危险的伴随情况。它既能引发又能加重急性呼吸窘迫综合征(ARDS),目前唯一的预防或治疗方法一直是采用经验性的所谓肺保护性通气设置,试图保护肺组织免受机械通气治疗不可避免带来的机械应力。患者的虚弱状态限制了临床药物研究,促使在动物模型中进行药物研发。小鼠和大鼠常被选作小动物模型,约占所有实验动物研究的95%,因为它们的生理机能可模拟人类情况。小鼠在机械通气研究中一直是更受欢迎的选择,但由于技术问题,使用大鼠有一些优势,因为它们体型大得多。在这些模型中诱导VILI和ARDS可能具有挑战性,而且用于产生与人类相似组织损伤的损伤的急性性质不一定能完全反映临床实际情况。本综述的目的是分析和总结该领域近期出版物中的方法,描述采用了哪些方法来模拟这些情况,可能找到一条共同途径以便比较各研究结果。然而,该研究表明研究人员采用的方法多种多样,导致结果比较困难,这或许意味着应采用更标准化的方法。

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本文引用的文献

1
Protective effect of apelin-13 on ventilator-induced acute lung injury.Apelin-13 对呼吸机相关性急性肺损伤的保护作用。
Mol Biol Rep. 2024 Jan 4;51(1):74. doi: 10.1007/s11033-023-08911-6.
2
Acute Respiratory Distress Syndrome; A Review of Recent Updates and a Glance into the Future.急性呼吸窘迫综合征:近期进展回顾与未来展望
Diagnostics (Basel). 2023 Apr 24;13(9):1528. doi: 10.3390/diagnostics13091528.
3
Mechanical power: meaning, uses and limitations.机械动力:含义、用途及局限性。
Intensive Care Med. 2023 Apr;49(4):465-467. doi: 10.1007/s00134-023-06991-3. Epub 2023 Mar 8.
4
The Wnt/β-catenin pathway regulates inflammation and apoptosis in ventilator-induced lung injury.Wnt/β-catenin 通路调节呼吸机诱导肺损伤中的炎症和细胞凋亡。
Biosci Rep. 2023 Mar 31;43(3). doi: 10.1042/BSR20222429.
5
Individualizing mechanical ventilation: titration of driving pressure to pulmonary elastance through Young's modulus in an acute respiratory distress syndrome animal model.个体化机械通气:通过急性呼吸窘迫综合征动物模型中的杨氏模量来滴定驱动压至肺弹性。
Crit Care. 2022 Oct 18;26(1):316. doi: 10.1186/s13054-022-04184-w.
6
MiR-9a-5p alleviates ventilator-induced lung injury in rats by inhibiting the activation of the MAPK signaling pathway via CXCR4 expression downregulation.miR-9a-5p 通过下调 CXCR4 表达抑制 MAPK 信号通路的激活,从而减轻大鼠呼吸机所致肺损伤。
Int Immunopharmacol. 2022 Nov;112:109288. doi: 10.1016/j.intimp.2022.109288. Epub 2022 Sep 30.
7
Exaggerated Ventilator-Induced Lung Injury in an Animal Model of Type 2 Diabetes Mellitus: A Randomized Experimental Study.2型糖尿病动物模型中夸大的呼吸机诱导性肺损伤:一项随机实验研究。
Front Physiol. 2022 Jun 6;13:889032. doi: 10.3389/fphys.2022.889032. eCollection 2022.
8
Lung-Protective Ventilation Attenuates Mechanical Injury While Hypercapnia Attenuates Biological Injury in a Rat Model of Ventilator-Associated Lung Injury.在呼吸机相关性肺损伤大鼠模型中,肺保护性通气可减轻机械性损伤,而高碳酸血症可减轻生物性损伤。
Front Physiol. 2022 Apr 21;13:814968. doi: 10.3389/fphys.2022.814968. eCollection 2022.
9
Punicalagin suppresses inflammation in ventilator-induced lung injury through protease-activated receptor-2 inhibition-induced inhibition of NLR family pyrin domain containing-3 inflammasome activation.鞣花酸通过抑制蛋白酶激活受体-2 诱导的 NOD 样受体家族含 pyrin 结构域蛋白 3 炎性小体激活来抑制呼吸机相关性肺损伤中的炎症。
Chem Biol Drug Des. 2022 Aug;100(2):218-229. doi: 10.1111/cbdd.14059. Epub 2022 May 4.
10
Lung damage created by high tidal volume ventilation in rats with monocrotaline-induced pulmonary hypertension.野百合碱诱导肺动脉高压大鼠大潮气量通气所致肺损伤。
BMC Pulm Med. 2022 Mar 5;22(1):78. doi: 10.1186/s12890-022-01867-6.