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Comprehensive standardized lung fibrosis modeling platform: multi‑pathway–induced model generation, providing precise support for evaluating the efficacy of novel drugs targeting pulmonary fibrosis.

Pulmonary fibrosis ( pulmonary fibrosis, PF ) is a group of diffuse pulmonary interstitial diseases characterized by destructive, irreversible damage. Their etiology is extremely complex and their pathogenic mechanisms remain unclear, often leading to pulmonary dysfunction and respiratory failure. Currently, there are no effective treatments, and the prognosis is exceedingly poor. Therefore, establishing a stable, reliable, and user-friendly model is crucial for deep… Exploring its pathogenesis and identifying effective therapeutic agents is of great significance.

 

Common animal models of pulmonary fibrosis

 

At present, many inducers are used in model making, such as Bleomycin, paraquat, hyperoxia, asbestos, and ionizing radiation, among others. All can cause lung injury, ultimately leading to pulmonary fibrosis.

 

Among them Bleomycin Most commonly used. Bleomycin is an aminoglycopeptide antibiotic isolated from the culture broth of Streptomyces verticilli, exhibiting potent antitumor activity and serving as a first-line anticancer agent; however, its adverse effects can lead to pulmonary fibrosis and associated clinical manifestations. 02

 

Protocol for Establishing a Mouse Model of Pulmonary Fibrosis

 

 

Aniphe BioLab Bleomycin-Induced Case Presentation:

 

| Laboratory Animals

 

C57 male, 10–12 weeks old.

 

| Modeling Method

 

01  An intratracheal instillation model was established. After anesthesia, the mice were placed on a tracheal intubation platform, and their limbs were secured with medical tape to maintain an upright posture.

02  The trachea is identified using a laryngoscope, and an indwelling needle is advanced along the trachea into the airway to administer the bleomycin working solution via airway instillation. 50 µL per animal).

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

 

| Experimental Evaluation System

 

① Lung coefficient ：

 

Weigh the lung tissue and calculate the lung coefficient; the lung coefficient ( % = Lung mass (g) / Body mass (g) × 100%.

 

② Lung HE staining ：

 

After the experiment, mouse lung tissues were collected and fixed for use in… H&E staining.

 

| Experimental Evaluation System

 

① Pathological tissue ：

 

 

  ② CT findings show ：


Lungs of mice in the model group On CT imaging, areas of consolidation and fibrotic bands are evident, appearing as more dense opacifications and linear structures—findings that reflect the replacement of normal lung parenchyma by fibrotic tissue. Compared with the control group, the model group exhibited reduced lung lobes and disorganized alveolar architecture, indicating that pulmonary fibrosis leads to decreased lung volume and disruption of lung structure.

 

 

② HE results show:

 

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.

 

 

| Model Features:

 

Intratracheal administration of bleomycin can It directly damages alveolar epithelial cells, and a single administration is sufficient to induce fibrosis within a short time.

 

| Other induction methods

 

① Induced by blight Pulmonary fibrosis model

 

Studies have shown that intraperitoneal injection 20mg/kg (Rat) or 10mg/kg After a certain period, the model can be established. 5-9d Occur, 2-3 (Reaches a peak at week 4). Paraquat can also be administered orally in high doses to establish the model: oral administration. 50mg/kg after 120h This leads to pulmonary fibrosis.

 

The pathogenesis is that, after being absorbed into the body, Through complex biochemical processes, large amounts of oxygen free radicals are generated, leading to lipid peroxidation in organ and tissue cells and subsequently inducing tissue fibrosis. Alveolar cells exhibit strong active uptake and accumulation of paraquat; consequently, the lungs suffer the most severe damage and are highly susceptible to triggering pulmonary fibrosis.

 

② Amiodarone-induced pulmonary fibrosis model

 

Amiodarone ( amiodarone ， AD) It is a highly effective antiarrhythmic agent that is associated with a variety of adverse reactions; studies have shown that, AD The pulmonary toxicity thus induced is primarily characterized by the accumulation of foamy cells within the alveolar spaces. II Proliferation of type II alveolar epithelial cells and pulmonary interstitial fibrosis.

 

There is research. Adopted daily 1 Next, consecutive 5 d Intratracheal injection 0 . 1 ml Amiodarone hydrochloride ( 1 . 25 mg) Using the saline method, a rat model of amiodarone-induced pulmonary toxicity was established. Results: The… 28 At this stage, fibroblasts around the blood vessels and bronchi proliferate extensively, with a marked increase in collagen deposition; collagen fibers within the surrounding lung parenchyma are also markedly augmented, and numerous foam cells are observed in clusters. The alveolar septa are widened, II Alveolar cell hyperplasia is prominent, and pulmonary fibrosis develops.

 

③ Oleic acid–induced pulmonary fibrosis model

 

The mechanisms underlying oleic acid–induced pulmonary fibrosis are primarily : Under the influence of inflammatory mediators and chemokines, neutrophils are stimulated to adhere, undergo chemotaxis, and migrate to the site of inflammation, where they carry out phagocytosis, degranulation, and the respiratory burst, releasing lysosomal enzymes and reactive oxygen species along with a host of other metabolic products. While eliminating the inflammatory agents, these processes also inflict tissue damage; meanwhile… Raise MDA Causes protein cross-linking and denaturation, DNA Fibrosis disrupts the structural integrity of lung tissue, stimulates the progressive proliferation of fibrous tissue, and ultimately triggers pulmonary fibrosis.

 

④ 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.

 

⑤ Asbestos-induced pulmonary fibrosis model

 

Asbestos particles are a type of occupational environmental toxin, Inhalation into the alveoli induces localized alveolar inflammation and triggers the release of cytokines, leading to… It induces fibroblast proliferation and the release of abundant extracellular matrix, which, through repeated stimulation, ultimately triggers pulmonary fibrosis. Some studies have… 1 ml 20 g·L - 1 Asbestos‑induced pulmonary fibrosis was successfully established in rats by directly instilling asbestos‑containing saline into the lungs via a laryngoscope inserted into the trachea, followed by gentle massage of both lungs for a brief period.

 

⑤ 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. Some studies have employed SIEMENS Primus Hi High-energy linear accelerator, single‑fraction whole‑lung irradiation through the anterior chest in mice, planar view. 12 Gy Conduct research on a mouse model of pulmonary fibrosis, and the results… Masson Staining shows the irradiated group small The lung tissue of rats after irradiation 4 Collagen fiber deposition begins around week , whereas in 16 and 24 Under light microscopy, distinct focal areas of fibrosis were observed, indicating successful establishment of the pulmonary fibrosis model.

 

Summary

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.

Aniphe BioLab offers a variety of approaches to establish pulmonary fibrosis models and provides pharmacological and efficacy evaluation services for related disease models. We welcome all clients to contact us for more information!

 

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