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

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, but a progressive disease of the lung. The method of constructing an animal model is the groundwork for this consecutive research. How to build a typical human mimicking animal model remains challenging. Thus, to reveal the mechanism and to make it useful for IPF clinical treatment, this study aimed to use a different type of IPF mice model and use several inspection methods to evaluate which one is more applicable for the study of IPF. Twelve-week-old C57BL/6 mice were divided into 3 type groups, as intraperitoneal injection, intratracheal administration, and intravenous administration of bleomycin (BLM) to initiate lung fibrosis. Lung PET/CT of BLM-receiving mice showed an increase in fibrotic consolidations compared with that of saline control mice. CT quantification showed an increase in mean lung density in BLM-treated mice compare with that of saline controls. TGF-1, TNF-, IL-6, GM-CSF in BALF(Bronchoalveolar Lavage Fluid) and serum.PAI-1, HYP in the lung tissue of mice were significantly different in each BLM groups than those in the saline control group. The results of Masson staining in mice indicate that the lung tissues of the tracheal perfusion group, the intravenous injection group, and the intraperitoneal injection group have a higher degree of pulmonary septal thickening and collagen fiber consolidation. The intratracheal group is more advanced than the other groups. Picro-Sirius red 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 and disintegrated, exfoliated endothelial cells were swelling, type II alveolar epithelial cells were proliferated, abundant microvilli were on the free surface of the cell, vacuolar degenerated in the intracellular lamellar bodies, the shape of the nucleus was irregular, and some tooth-like protrusions were seen. Based on the comparison of three different methods of animal model construction, high dose of each shows more compliable, and BLM can successfully induce animal models of pulmonary fibrosis, however, there are certain differences in the fibrosis formation sites of them three, and tail vein injection of BLM induced pulmonary fibrosis 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 Frontiers in Pharmacology frontiersin.org pulmonary fibrosis were also evident in the previous studies (Demirkol et al, 2023;Gul et al, 2023). Significantly, the outcomes of this study underscore the effectiveness of Capsaicin treatment in improving the macroscopic lung characteristics as well as the histopathological distortions induced by Bleomycin in a comparable and even more substantial restorative effect when compared to the commercially available antifibrotic drug, Pirfenidone.…”

Nuclear accumulated μ-calpain in AT2 cell participates in pulmonary fibrosis via inactivating FoxO3a

“…Same amount of saline was delivered to the mice as a control. At day 21, mice were euthanized, and the lung tissue was harvested [27].…”

The mitigating effect of para‐hydroxycinnamic acid in bleomycin‐induced pulmonary fibrosis in mice through targeting oxidative, inflammatory and fibrotic pathways

“…One of the limitations of this study was the animal strain; the BALB/c mouse strain was the only available mouse strain in the country, where the majority of available literature and research papers use C57bl/6 because they are very susceptible to BLM insult at low doses (4 IU/kg or lower) using different routes of delivery. 63,64 Still, BALB/c mice are being widely used to study PF. Still, a higher dose of BLM as high as 5 mg/kg, equivalent to 7.5 IU/kg, should be used as single or multiple administrations to establish a pulmonary injury.…”