A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization
January 20th, 2023
Various animal models of pulmonary fibrosis have been established using bleomycin to clarify the pathogenesis of pulmonary fibrosis and find new drug targets. However, most pulmonary fibrosis models targeting lung tissue have uneven drug administration. Here, we propose a model of uniform pulmonary fibrosis induced by nasal bleomycin nebulization.
In this study, inter-pulmonary administration of Bleomycin is carried out by nasal nebulization to create a mouse model of pulmonary fibrosis that closely mimic clinical disease characteristics. After anesthetizing the mouse press its toes with the index finger and thumb to ensure the limb withdrawal reflects has disappeared. Once the instrument is calibrated, secure the anesthetized mouse with a soft mesh cover.
Using a pipette, add the working BLM solution to the top atomizing head of the exposure tower, and run the nebulizer for 30 minutes to achieve stable atomization. Now double click the FlexiWare 8 icon. Select the Experimentation Session and click the New Study button.
Edit the Experiment Name, Title, and Owner. Then choose the IX-4DIO template. Input the operator and click the Confirm button.
Click Next In the Welcome window. In the Pump Selection window, choose the Pump tab and click Next. It leads to the window named, Test set-up-Pump 4.
Click the Next button and the Pump Output Adjustment window will pop up, and click Next again. Then click the Finish button in the Results-Pump 4 window. Click on the settings for Continuous 1L/min.
Select DIO1 and set the Duty Cycle to 25%Then click OK and set the Duty Cycle percent for DIO2, DIO3, and DIO4. Now start the procedure by clicking the top green button and stop by clicking the red button. Click X at the top right corner to quit.
The BLM administered mice lungs displayed diffused pneumonic lesions with loss of the normal alveolar architecture, septal thickening, enlarged alveoli, and increased infiltration of inflammatory cells into the Interstitial and Peribronchiolar areas, compared to the control group. The Ashcroft scores for the BLM mice on the 9th, 16th and 23rd days, were higher than those in the control group. The aerosolized the particle with 2.5 to four micrometer in size, which enable Bleomycin to distribute evenly throughout the lung and that reach the subpleural area.
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Overview
The study introduces a novel model for pulmonary fibrosis using nasal nebulization of bleomycin, allowing for uniform drug distribution in the lungs. This model closely mimics clinical disease characteristics and aids in understanding the pathogenesis of pulmonary fibrosis.
Key Study Components
Research Area
- Pulmonary fibrosis
- Drug delivery mechanisms
- Animal modeling
Background
- Incident pulmonary fibrosis often results in significant morbidity.
- Current models show uneven drug administration affecting results.
- Understanding drug delivery can enhance therapeutic strategies.
Methods Used
- Nasal nebulization of bleomycin for inter-pulmonary administration.
- Mouse model for experimental evaluation.
- Aerosol particle size optimization for effective distribution.
Main Results
- Mice treated with bleomycin exhibited pneumonic lesions and loss of normal alveolar architecture.
- Increased infiltration of inflammatory cells was observed.
- The Ashcroft scores indicated significant fibrosis compared to control groups.
Conclusions
- This study demonstrates an effective method for inducing uniform pulmonary fibrosis.
- The model provides insights into drug targeting and disease mechanisms.
