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Pulmonary fibrosis (PF) animal model

Pulmonary fibrosis (PF) animal model

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Idiopathic pulmonary fibrosis
Psychiatric & neurological disease models

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Model Introduction

Model Introduction

Platform Service Advantages

Platform Service Advantages

Experimental results

Experimental results

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Idiopathic pulmonary fibrosis

Introduction to the PF Animal Model

Pulmonary fibrosis (PF) is a diffuse interstitial lung disease characterized by destructive, irreversible tissue damage. Its etiology is highly complex and its pathogenic mechanisms remain unclear; it can lead to impaired pulmonary function and respiratory failure, with no effective treatment currently available and a very poor prognosis. Therefore, establishing a stable, reliable, and easily reproducible animal model is crucial for elucidating its pathogenesis and identifying novel therapeutic agents. Numerous inducers have been employed in model‑generation studies; examples include bleomycin, paraquat, hyperoxia, asbestos, and ionizing radiation, all of which can induce lung injury and ultimately result in pulmonary fibrosis. Among these, bleomycin is the most widely used. Bleomycin is an aminoglycoside antibiotic isolated from the culture broth of Streptomyces verticillus, exhibiting potent antitumor activity and serving as a first‑line anticancer agent; however, its adverse effects can precipitate pulmonary fibrosis and associated clinical manifestations.

Advantages of Aniphe BioLab’s PF Animal Model Platform Services

Leveraging established pulmonary fibrosis model‑building techniques and a robust pharmacological evaluation platform, we provide high‑quality experimental support for the development of anti‑fibrotic therapeutics and for mechanistic studies.

Comprehensive model coverage

Maturity Model Framework

It encompasses classic pulmonary fibrosis models, such as the bleomycin‑induced model, with stable and highly reproducible experimental outcomes.

Standardization of the modeling process

Multidimensional Efficacy Evaluation

It supports multi‑parameter analysis, including histopathology, collagen deposition, inflammatory cytokines, and molecular biology.

Multidimensional Evaluation System

Personalized Plan Design

The modeling cycle, administration route, and evaluation metrics can be customized to meet research requirements.

Standardization of Data Delivery

Standardized Quality Control

Standardize experimental procedures to ensure model robustness and data reliability, thereby supporting scientific research and innovative drug development.

Modeling cycle

2-3 weeks

1  Laboratory animals

C57 male mice

1  Positive drug

Pirfenidone and Nintedanib

1  Application areas

It is applied in research on the pathogenesis of pulmonary fibrosis, screening for anti-fibrotic drugs, validation of therapeutic targets, investigation of the mechanisms underlying inflammation and tissue repair, as well as in cell therapy, gene therapy, and the evaluation of the efficacy of innovative therapeutics.

Experimental results

Construction of a PF animal model

01 A model was established by intratracheal instillation of bleomycin. After anesthesia, the mice were placed on a tracheal intubation platform, their limbs were secured with medical tape, and they were maintained in an upright position.

02 The trachea is identified using a laryngoscope, and the indwelling needle is advanced along the trachea into the airway to administer the bleomycin working solution via airway instillation.

03 After the mice have recovered from anesthesia, return them to their cages and provide jelly to replenish fluids and nutrients.

Model characteristics: Intratracheal administration of bleomycin can directly injure alveolar epithelial cells, and a single dose is sufficient to induce fibrosis within a short time.

Pathological tissue

The lung tissue as a whole appears pink, with areas of congestion and uneven coloration; the texture is coarse and somewhat firm, suggesting the presence of inflammatory and fibrotic changes—typical findings for subsequent pathological analysis.

 

 

Pathological tissue; image source: Aniphe BioLab.

CT scan results

On chest CT images, mice in the model group exhibited areas of consolidation and fibrotic bands, manifesting as more densely opacified regions and linear structures—findings attributable to the replacement of normal lung tissue by fibrotic tissue. Compared with the control group, the model group showed reduced lung lobes and disorganized alveolar architecture, indicating that pulmonary fibrosis leads to a decrease in lung volume and disruption of lung structure.

 

 

CT scan results; image courtesy of Aniphe BioLab.

HE staining results

In the control group, the lung tissue architecture was intact, with no obvious inflammatory cells or fibrotic lesions observed; in the model group, mice exhibited marked disruption of lung tissue structure, significant thickening of alveolar walls, and the development of inflammatory infiltrates.

 

 

HE staining results; image source: Aniphe BioLab.

Treatment data for pirfenidone (PFD) and nintedanib (NDN)

01 The results of inflammatory cell counts in bronchoalveolar lavage fluid showed that, following bleomycin (BLM)-induced pulmonary fibrosis, mice exhibited a marked accumulation of various inflammatory cell types in the lungs. Treatment with pirfenidone and nintedanib significantly reduced the number of inflammatory cells; both clinically approved antifibrotic agents attenuated pulmonary inflammation, with nintedanib demonstrating a more potent anti-inflammatory effect.

 

 

02 ELISA results showed that in the bleomycin‑induced mouse model, proinflammatory cytokines IL‑1β, IL‑4, and IL‑6 were markedly elevated, while IFN‑γ was decreased; treatment with pirfenidone and nintedanib significantly reduced proinflammatory cytokine levels and restored IFN‑γ concentrations. Both drugs ameliorated pulmonary inflammatory imbalance, with nintedanib demonstrating a more pronounced effect.

 

 

03 Oxidative Stress and Neutrophil Markers: The results showed that in bleomycin‑induced mouse models, pulmonary antioxidant capacity was reduced, oxidative damage was increased, and neutrophil activation was significantly elevated. Pirfenidone and nintedanib both effectively increased superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) and myeloperoxidase (MPO) levels, thereby alleviating pulmonary oxidative stress–related injury; the effects of nintedanib were more pronounced.

 

 

04 Quantitative analysis of hydroxyproline revealed a significant increase in pulmonary collagen content in bleomycin‑induced mouse models. Pirfenidone and nintedanib reduced pulmonary collagen deposition across all four administration regimens—early prevention, early/late treatment, and continuous intervention—and nintedanib exhibited a more pronounced anti‑fibrotic effect during the late fibrotic stage.

 

 

05 Hematoxylin–eosin staining of lung tissue revealed disorganized alveolar architecture, extensive interstitial inflammation, and fibrotic lesions in bleomycin‑induced mouse models. Pirfenidone and nintedanib attenuated alveolar damage and interstitial pathology, with greater efficacy when administered early or throughout the course of treatment; in the late fibrotic stage, nintedanib demonstrated a more pronounced protective effect on lung tissue.

 

 

06 Quantitative analysis of fibrotic area revealed a significant increase in the proportion of pulmonary fibrotic lesions in bleomycin‑induced mouse models. Both pirfenidone and nintedanib reduced fibrotic area; early intervention yielded comparable efficacy, whereas in advanced fibrosis and under a continuous administration regimen, nintedanib demonstrated a more pronounced inhibitory effect on fibroproliferation.

 

 

References: Comparative efficacy of pirfenidone and nintedanib in inhibiting bleomycin‑induced pulmonary fibrosis in mice

 

Other induction methods

The methods for establishing animal models of pulmonary fibrosis have become increasingly diverse, and the associated techniques have grown ever more sophisticated. Selecting an appropriate model is of great significance for investigating the pathological processes and pathogenic mechanisms of pulmonary fibrosis.

01 Bleomycin-induced pulmonary fibrosis model

Studies have shown that intraperitoneal injection of 20 mg/kg in rats or 10 mg/kg in mice can induce the model after a certain period (onset within 5–9 days, reaching a peak at 2–3 weeks). Alternatively, a high oral dose of bleomycin can be used to establish the model: administration of 50 mg/kg by gavage leads to pulmonary fibrosis within 120 hours.

The pathogenic mechanism involves the substance, upon absorption into the body, undergoing complex biochemical processes that generate large quantities of oxygen free radicals, leading to lipid peroxidation in organ and tissue cells and subsequently inducing tissue fibrosis. Alveolar cells exhibit a strong active uptake and accumulation of paraquat; consequently, the lungs suffer the most severe damage and are particularly prone to developing pulmonary fibrosis.

02 Amiodarone-induced pulmonary fibrosis model

Amiodarone (AD) is a highly effective antiarrhythmic agent that is associated with a variety of adverse reactions. Studies have shown that amiodarone‑induced pulmonary toxicity primarily manifests as alveolar space–filled foam cell accumulation, type II pneumocyte hyperplasia, and pulmonary interstitial fibrosis.

One study established a rat model of amiodarone‑induced pulmonary toxicity by administering 0.1 mL of amiodarone hydrochloride (1.25 mg) in saline via intratracheal instillation once daily for five consecutive days. On day 28, marked proliferation of fibroblasts was observed around blood vessels and bronchi, with a significant increase in collagen deposition; collagen fibers within the surrounding lung parenchyma were also markedly augmented, accompanied by extensive aggregates of foam cells. Alveolar septal thickening was evident, type II pneumocytes showed prominent hyperplasia, and pulmonary fibrosis had developed.

03 Oleic acid–induced pulmonary fibrosis model

The mechanisms underlying oleic acid–induced pulmonary fibrosis are primarily as follows: under the influence of inflammatory mediators and chemokines, neutrophils are activated to adhere to endothelial surfaces, migrate toward the site of inflammation, and engage in phagocytosis, degranulation, and the respiratory burst, thereby releasing lysosomal enzymes, reactive oxygen species, and a host of other metabolic products. While these processes eliminate pathogenic stimuli, they also inflict tissue damage. Concurrently, elevated levels of malondialdehyde (MDA) promote protein cross-linking and denaturation, as well as DNA fragmentation, disrupting the structural integrity of lung tissue and stimulating the progressive proliferation of fibrous tissue, ultimately culminating in pulmonary fibrosis.

04 Silica-Induced Pulmonary Fibrosis Model

Silica dust is an industrial particulate that, upon long-term inhalation, can cause severe pulmonary damage. At present, the use of silica to establish pulmonary injury models is primarily focused on replicating silicosis. Typically, such models are generated by directly instilling a silica suspension into the trachea of experimental animals.

05 Asbestos-Induced Pulmonary Fibrosis Model

Asbestos particles are a class of occupational environmental toxins that, upon inhalation into the alveoli, induce localized alveolar inflammation, trigger the release of cytokines, stimulate fibroblast proliferation and the secretion of abundant extracellular matrix, and—through repeated exposure—ultimately precipitate pulmonary fibrosis. In one study, 1 mL of an asbestos‑saline suspension at a concentration of 20 g·L⁻¹ was directly instilled into the lungs of rats via a laryngoscope inserted into the trachea, followed by gentle massage of both lungs for a brief period, thereby successfully establishing a rat model of pulmonary fibrosis.

06 Radiation-Induced Pulmonary Fibrosis Model

In the course of scientific research on how to prevent and treat radiation‑induced lung injury, it is essential to establish relevant animal models of radiation‑induced pulmonary fibrosis. One study utilized a SIEMENS Primus Hi high‑energy linear accelerator to deliver a single anterior thoracic field irradiation of 12 Gy to the lungs of mice, thereby establishing a murine model of pulmonary fibrosis. Masson’s trichrome staining revealed that collagen fiber deposition began in the lung tissue of the irradiated group approximately four weeks after exposure, and by weeks 16 and 24, distinct focal areas of fibrosis were readily observable under light microscopy, indicating successful establishment of the pulmonary fibrosis model.