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

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

doi:10.1186/s42826-025-00235-9

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

Lab Anim Res. 2025 Jan 24;41(1):4. doi: 10.1186/s42826-025-00235-9.

Authors

Kuo-An Chu^{1

2

3

4}, Chia-Yu Lai⁵, Yu-Hui Chen⁵, Fu-Hsien Kuo⁵, I-Yuan Chen¹, You-Cheng Jiang¹, Ya-Ling Liu¹, Tsui-Ling Ko⁶, Yu-Show Fu⁷

Affiliations

¹ Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC.
² School of Medicine, College of Medicine, National Sun Yat-Sen University, No. 70, Lienhai Rd., Kaohsiung, Taiwan, ROC.
³ School of Nursing, Fooyin University, Kaohsiung, Taiwan, ROC.
⁴ Department of Nursing, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan, ROC.
⁵ Institute of Anatomy and Cell Biology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.
⁶ School of Medicine, College of Medicine, National Sun Yat-Sen University, No. 70, Lienhai Rd., Kaohsiung, Taiwan, ROC. kate819b@g-mail.nsysu.edu.tw.
⁷ Department of Anatomy and Cell Biology, School of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Li-Nung Street, Taipei, Taiwan, ROC. ysfu@nycu.edu.tw.

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.

Keywords: Acute lung injury; Acute respiratory distress syndrome (ARDS); Animal model; Arterial oxygen saturation (SpO2); Cell infiltration; Cytokine storm; Partial arterial pressure of oxygen (PaO2).

Abstract

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