Model Introduction
The Pulmonary Fibrosis (PF) animal model is an experimental system where lung tissue is induced to produce a large number of abnormally activated fibroblasts, tissue remodeling, and excessive deposition of extracellular matrix (ECM) proteins (such as collagen) through physical, chemical, or biological means. This model aims to highly simulate the pathological characteristics of human interstitial lung disease, serving as a core foundation for revealing pathogenic mechanisms, screening biomarkers, and evaluating clinical therapeutic strategies.
Research Applications
This model is primarily used for:
- Simulating the occurrence and evolution of human pulmonary fibrosis to study its molecular pathogenesis.
- Screening and validating specific biomarkers for pulmonary fibrosis.
- Evaluating the efficacy and safety of anti-fibrotic drugs, clinical treatment strategies, and innovative therapies.
Experimental Design Key Points
- Bleomycin (BLM) Induction Method:
- Intravenous injection (tail vein): A single dose of 200 mg/kg typically reaches peak fibrosis at week 4.
- Intratracheal injection: A single dose of 5 mg/kg results in deteriorated lung function and right ventricular hypertrophy observable after 35 days.
- Intranasal instillation: Mice are anesthetized and fixed in a supine position with the head elevated by 30°. A micropipette is used to slowly drop the BLM solution into a single nostril to ensure spontaneous inhalation; the tilted posture is maintained for 1 minute post-administration.
- Hyperoxia Induction Method:
- Parameter Settings: Oxygen concentration is typically 70%-90% (85% is commonly used); temperature 22-25°C, humidity 40-60%; CO₂ absorbers must be used (target CO₂ < 0.5%).
- Duration: 3-7 days for acute injury exposure; 14-28 days for chronic fibrosis exposure.
- Operational Standard: The chamber opening time must be less than 30 minutes daily to avoid drastic fluctuations in oxygen concentration.
- Other Inducing Factors:
- Environmental factors: Exposure to silica or asbestos.
- Biological factors: Overexpression of specific cytokines via gene editing, or targeting type II alveolar epithelial cell injury using antibodies/drugs.
- Drugs/Toxins: Amiodarone, oleic acid, paraquat, etc.
Key Monitoring Indicators
- Pathological Evaluation:
- Tissue Staining: H&E staining to assess the degree of alveolitis; Masson’s trichrome staining to assess the degree of fibrosis.
- Biochemical Testing: Hydroxyproline assay to evaluate collagen content in lung tissue.
- Imaging Evaluation:
- Micro-CT: Quantification of the extent and severity of pulmonary fibrosis.
- PET Imaging: Non-invasive assessment of lung tissue remodeling.
- Functional Evaluation:
- Pulmonary Function Testing: Using the FlexiVent system to evaluate inspiratory capacity and compliance.
- Molecular Biology Evaluation:
- Marker Detection: Expression levels of TGF-β1, α-SMA, and Type I collagen.
- Inflammatory Analysis: Concentration of inflammatory cytokines in Bronchoalveolar Lavage Fluid (BALF).
- General Signs Monitoring:
- Daily recording of body weight, respiratory rate, survival rate, and activity status (e.g., hunched posture under hyperoxia).
