An animal model of severe acute respiratory distress syndrome for translational research

Abstract Background Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine. Whether the pathology of animal models with acute lung injury in p...

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Main Authors: Kuo-An Chu, Chia-Yu Lai, Yu-Hui Chen, Fu-Hsien Kuo, I.-Yuan Chen, You-Cheng Jiang, Ya-Ling Liu, Tsui-Ling Ko, Yu-Show Fu
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Laboratory Animal Research
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Online Access:https://doi.org/10.1186/s42826-025-00235-9
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author Kuo-An Chu
Chia-Yu Lai
Yu-Hui Chen
Fu-Hsien Kuo
I.-Yuan Chen
You-Cheng Jiang
Ya-Ling Liu
Tsui-Ling Ko
Yu-Show Fu
author_facet Kuo-An Chu
Chia-Yu Lai
Yu-Hui Chen
Fu-Hsien Kuo
I.-Yuan Chen
You-Cheng Jiang
Ya-Ling Liu
Tsui-Ling Ko
Yu-Show Fu
author_sort Kuo-An Chu
collection DOAJ
description Abstract Background Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine. Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of transplanted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency. Results In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within seven days after the injury, we found that arterial blood oxygen saturation (SpO2) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2) amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A histological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7. Conclusions This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.
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spelling doaj-art-ff4dd51ae7e741458c2477267d6252d92025-01-26T12:12:46ZengBMCLaboratory Animal Research2233-76602025-01-0141111210.1186/s42826-025-00235-9An animal model of severe acute respiratory distress syndrome for translational researchKuo-An Chu0Chia-Yu Lai1Yu-Hui Chen2Fu-Hsien Kuo3I.-Yuan Chen4You-Cheng Jiang5Ya-Ling Liu6Tsui-Ling Ko7Yu-Show Fu8Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General HospitalInstitute of Anatomy and Cell Biology, School of Medicine, National Yang Ming Chiao Tung UniversityInstitute of Anatomy and Cell Biology, School of Medicine, National Yang Ming Chiao Tung UniversityInstitute of Anatomy and Cell Biology, School of Medicine, National Yang Ming Chiao Tung UniversityDivision of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General HospitalDivision of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General HospitalDivision of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General HospitalSchool of Medicine, College of Medicine, National Sun Yat-Sen UniversityDepartment of Anatomy and Cell Biology, School of Medicine, National Yang Ming Chiao Tung UniversityAbstract Background Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine. Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of transplanted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency. Results In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within seven days after the injury, we found that arterial blood oxygen saturation (SpO2) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2) amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A histological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7. Conclusions This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.https://doi.org/10.1186/s42826-025-00235-9Acute respiratory distress syndrome (ARDS)Animal modelAcute lung injuryArterial oxygen saturation (SpO2)Partial arterial pressure of oxygen (PaO2)Cytokine storm
spellingShingle Kuo-An Chu
Chia-Yu Lai
Yu-Hui Chen
Fu-Hsien Kuo
I.-Yuan Chen
You-Cheng Jiang
Ya-Ling Liu
Tsui-Ling Ko
Yu-Show Fu
An animal model of severe acute respiratory distress syndrome for translational research
Laboratory Animal Research
Acute respiratory distress syndrome (ARDS)
Animal model
Acute lung injury
Arterial oxygen saturation (SpO2)
Partial arterial pressure of oxygen (PaO2)
Cytokine storm
title An animal model of severe acute respiratory distress syndrome for translational research
title_full An animal model of severe acute respiratory distress syndrome for translational research
title_fullStr An animal model of severe acute respiratory distress syndrome for translational research
title_full_unstemmed An animal model of severe acute respiratory distress syndrome for translational research
title_short An animal model of severe acute respiratory distress syndrome for translational research
title_sort animal model of severe acute respiratory distress syndrome for translational research
topic Acute respiratory distress syndrome (ARDS)
Animal model
Acute lung injury
Arterial oxygen saturation (SpO2)
Partial arterial pressure of oxygen (PaO2)
Cytokine storm
url https://doi.org/10.1186/s42826-025-00235-9
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