Pulmonary fibrosis model of mice induced by different administration methods of bleomycin

Abstract

Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease of the lung. How to build a typical human mimicking animal model has been a challenge. Thus, to reveal the mechanism and to make it useful for IPF clinical treatment, a different type of mice model and inspection methods are used to evaluate which one is applicable for the study of IPF. Method 69 Twelve-weeks-old C57BL/6 mice were divided into 3 type groups (n = 7 for each control group, n = 8 for each BLM-induced pulmonary fibrosis groups), as intraperitoneal injection, intratracheal administration, and intravenous administration of bleomycin (BLM) to initiate lung fibrosis. Changes of the lung function measured through mice Pulmonary function test (PFT). Morphological changes in mice were observed by PET/CT, Masson and Picro-Sirius staining, Transmission electron microscopy (TEM). Biochemical changes were tested by Enzyme-linked immunosorbent assay (Elisa). Results PET/CT of BLM-receiving mice showed an increase in fibrotic consolidations and an increase in non-aerated lung area in BLM-treated mice compared with that in controls. TGF-b1, TNF-a, IL-6, GM-CSF in BALF and serum. PAI-1, HYP in the lung tissue of mice were significantly different in each BLM groups than those in the controls. The results of Masson staining in mice indicate that the lung tissues of all BLM received groups, the intratracheal groups, the intravenous groups, and the intraperitoneal groups have a higher degree of pulmonary septal thickening and collagen fiber consolidation compare to saline control. Picro-Sirius staining results are consistent with the results of Masson staining. Compared with the saline control group, the ratio of Col 1/Col 3 was significantly increased in each BLM group. TEM results found that in BLM group, type I alveolar epithelial cells were degenerated. Exfoliated endothelial cells were swelling, and type II alveolar epithelial cells were proliferated, the shape of the nucleus was irregular, and some tooth-like protrusions were seen. Conclusions With three different methods of animal model construction, high dose of each show more compliable, and BLM can successfully induce animal models of pulmonary fibrosis, however, certain differences in the fibrosis formation sites of them three, and tail vein injection of BLM induced PF model is closer to the idiopathic pulmonary interstitial fibrosis.

Capsaicin ameliorate pulmonary fibrosis via antioxidant Nrf-2/ PPAR- γ pathway activation and inflammatory TGF-β1/ NF-κB/COX II pathway inhibition

“…Additionally, there was an increase in collagen and mucin content. These features of bleomycin-induced pulmonary fibrosis were also evident in the previous studies ( Demirkol et al, 2023 ; Gul et al, 2023 ).…”

Anti-Inflammatory and Antifibrotic Potential of Longidaze in Bleomycin-Induced Pulmonary Fibrosis

“…The early stage of bleomycin-induced lung injury is manifested by acute inflammation, including alveolar epithelial damage, inflammatory cell infiltration, release of inflammatory mediators, and peripheral blood leukocytosis [ 33 ]. It should be noted that during the acute phase of bleomycin-induced inflammation, macrophages and lymphocytes migrate to the lungs.…”

Animals in Respiratory Research

“…Further, the bleomycin model does not produce all relevant changes in the mouse lung. The mouse bleomycin model is also a good example of the numerous influences in animal models, such as strain, age, sex, and route of administration [ 83 , 84 ]. Differences in species-specific cellular responses between mice and humans may explain translation problems in asthma [ 85 ].…”

“…The location of the lesions depends on the route of administration. After tail vein injection, fibrosis was concentrated under the pleura and evenly distributed in the interstitial space of the lung, while after intratracheal administration, lesions were concentrated around the trachea and unevenly distributed in different lobes of the lung [ 84 ]. Intraperitoneal injection leads to fibrosis mainly concentrated under the pleura and is more similar to the pathological distribution of clinical IPF than intratracheal administration.…”