Intratracheal Bleomycin Aerosolization: The Best Route of Administration for a Scalable and Homogeneous Pulmonary Fibrosis Rat Model?

• Main Authors: Alexandre Robbe, Alexandra Tassin, Justine Carpentier, Anne-Emilie Declèves, Zita Léa Mekinda Ngono, Denis Nonclercq, Alexandre Legrand
• Format: Article
• Language: English
• Published: Hindawi Limited 2015-01-01
• Series: BioMed Research International
• Online Access: http://dx.doi.org/10.1155/2015/198418
• ISSN: 2314-6133; 2314-6141

Idiopathic pulmonary fibrosis (IPF) is a chronic disease with a poor prognosis and is characterized by the accumulation of fibrotic tissue in lungs resulting from a dysfunction in the healing process. In humans, the pathological process is patchy and temporally heterogeneous and the exact mechanisms remain poorly understood. Different animal models were thus developed. Among these, intratracheal administration of bleomycin (BML) is one of the most frequently used methods to induce lung fibrosis in rodents. In the present study, we first characterized histologically the time-course of lung alteration in rats submitted to BLM instillation. Heterogeneous damages were observed among lungs, consisting in an inflammatory phase at early time-points. It was followed by a transition to a fibrotic state characterized by an increased myofibroblast number and collagen accumulation. We then compared instillation and aerosolization routes of BLM administration. The fibrotic process was studied in each pulmonary lobe using a modified Ashcroft scale. The two quantification methods were confronted and the interobserver variability evaluated. Both methods induced fibrosis development as demonstrated by a similar progression of the highest modified Ashcroft score. However, we highlighted that aerosolization allows a more homogeneous distribution of lesions among lungs, with a persistence of higher grade damages upon time.