Chu Kuo-An, Lai Chia-Yu, Chen Yu-Hui, Kuo Fu-Hsien, Chen I-Yuan, Jiang You-Cheng, Liu Ya-Ling, Ko Tsui-Ling, Fu Yu-Show
Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC.
School of Medicine, College of Medicine, National Sun Yat-Sen University, No. 70, Lienhai Rd., Kaohsiung, Taiwan, ROC.
Lab Anim Res. 2025 Jan 24;41(1):4. doi: 10.1186/s42826-025-00235-9.
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.
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 (SpO) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO) 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.
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.
尽管越来越多的研究致力于开发急性肺损伤的治疗方法，但在重症医学中，管理急性呼吸窘迫综合征（ARDS）仍然是一项挑战。先前研究中急性肺损伤动物模型的病理与ARDS的临床症状是否存在差异，导致对人类ARDS的管理存在疑问。为了精确评估移植干细胞或药物对急性肺损伤的治疗效果，我们开发了一种肺功能较低的严重ARDS动物模型，该模型能够使实验动物存活且具有一致的可重复性。建立这种动物模型有助于更高效地开发ARDS的治疗方法。
在这种方法中，我们通过与聚乙烯管相连的针头将博来霉素（BLM，5毫克/大鼠）经气管内注入大鼠左气管，并同时将大鼠向左旋转60度。在损伤后的七天内，我们发现动脉血氧饱和度（SpO）显著降至83.7%，动脉血氧分压（PaO）明显降至65.3毫米汞柱，动脉血二氧化碳分压（PaCO）升至49.2毫米汞柱，且呼吸频率随时间增加。形态学上，第1天左肺表面出现不均匀，第2天左肺肺泡消失，第7天左肺萎缩。组织学检查显示，第1天开始出现大量细胞浸润并持续至第7天，细胞浸润面积较大。第7天血清白细胞介素-5、白细胞介素-6、干扰素-γ、单核细胞趋化蛋白-1、巨噬细胞炎性蛋白-2、粒细胞集落刺激因子和肿瘤坏死因子-α水平大幅升高。
这种改良的博来霉素诱导肺损伤方法提供了一种严重、稳定且单侧（左叶）的具有一致可重复性的ARDS动物模型。在这种严重ARDS动物模型中观察到的生理症状与临床ARDS的特征完全一致。这种ARDS动物模型的建立有助于开发ARDS的治疗方法。
