Kodama Hiroshi, Takaki Haruyuki, Hirata Yutaka, Ueshima Eisuke, Kimura Yasushi, Wada Reona, Osuga Keigo, Yamakado Koichiro
Department of Radiology, Hyogo Medical University, Hyogo, Japan;
Department of Radiology, Hyogo Medical University, Hyogo, Japan.
In Vivo. 2025 Jan-Feb;39(1):251-256. doi: 10.21873/invivo.13823.
BACKGROUND/AIM: A standard mouse model of pulmonary fibrosis has been created by intratracheal or intraperitoneal administration of bleomycin. However, a difficulty presented by this traditional method is its high mortality rate of more than 50% after bleomycin administration. In this study, we aimed to establish a unilateral lung disease model and to assess its feasibility and usefulness.
After 6-week-old C57BL/6 mice were anesthetized, a 1.7Fr microcatheter was advanced into the trachea using an otoscope. Then, 1.0 mg/kg of bleomycin was injected into bilateral lung at the trachea (n=13) or unilateral lung (n=14) after advancing the microcatheter to the left main bronchus under fluoroscopy. Body weight change and survival of bilateral and unilateral lung disease group mice at day 28 were compared using Mann-Whitney and log-rank tests. Lungs were extracted and evaluated using Masson trichrome staining.
Body weights decreased 75.7%±14.0% in the bilateral lung disease group, but were greater, 94.1%±11.4%, in the unilateral lung disease group (p=0.03). Overall survival rates at day 28 were 30.8% and 85.7% in the bilateral and unilateral lung disease groups, respectively. Survival was significantly better in the unilateral lung disease model (p=0.01). Histological evaluation confirmed collagen deposition only in the bleomycin injected lung in the unilateral lung disease model.
Establishing both a healthy and a diseased lung in the same individual model was feasible, achieving lessened body weight loss and more favorable survival. This technique allows for a more efficacious research design, where both the efficacy and adverse effects of a pharmaceutical agent can be evaluated in a single animal.
背景/目的：通过气管内或腹腔内给予博来霉素已建立了肺纤维化的标准小鼠模型。然而，这种传统方法存在的一个问题是博来霉素给药后死亡率高达50%以上。在本研究中，我们旨在建立单侧肺部疾病模型并评估其可行性和实用性。
6周龄C57BL/6小鼠麻醉后，使用耳镜将1.7Fr微导管插入气管。然后，在荧光透视下将微导管推进到左主支气管后，向双侧肺（n = 13）或单侧肺（n = 14）注射1.0mg/kg博来霉素。使用Mann-Whitney和对数秩检验比较双侧和单侧肺部疾病组小鼠在第28天的体重变化和存活率。提取肺组织并使用Masson三色染色进行评估。
双侧肺部疾病组体重下降75.7%±14.0%，而单侧肺部疾病组体重下降幅度更大，为94.1%±11.4%（p = 0.03）。双侧和单侧肺部疾病组在第28天的总体存活率分别为30.8%和85.7%。单侧肺部疾病模型的存活率明显更高（p = 0.01）。组织学评估证实，在单侧肺部疾病模型中，仅在注射博来霉素的肺中出现胶原沉积。
在同一个体模型中建立健康肺和患病肺是可行的，可减轻体重减轻并提高存活率。该技术允许进行更有效的研究设计，即在单个动物中评估药物的疗效和不良反应。
