A new mouse model of biomass smoke-related chronic obstructive pulmonary disease combining porcine pancreatic elastase nebulization.

BACKGROUND

Biomass smoke exposure (BME) is an independent risk factor for chronic obstructive pulmonary disease (COPD), particularly among women and children in developing countries. Existing animal models of biomass smoke-related COPD are limited due to prolonged modeling periods. This study aimed to develop a novel composite protocol for constructing a biomass smoke-related COPD mouse model using porcine pancreatic elastase nebulization.

METHODS

Six-week-old female C57BL/6 mice (n=6 per group) were exposed to porcine pancreatic elastase nebulization on the first day and biomass smoke for the remaining 6 days of each week over a 4-month period. Pulmonary function, histopathology, and inflammatory markers were assessed via pulmonary function tests, Hematoxylin & eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA) and multiplexed liquid chip analysis respectively.

RESULTS

BME induced significant pulmonary function impairment, characterized by increased functional residual capacity (FRC), quasi-static compliance, and static compliance, alongside reduced a ratio of forced expiratory volume at 100 ms and forced vital capacity (FEV100/FVC), dynamic pulmonary compliance as well. Histopathological analysis revealed emphysema and bronchiectasis in lung tissue. Elevated levels of interleukin-1β (IL-1β) and interleukin-10 (IL-10) were observed in the BME group, with a concurrent increase in plasma interleukin-2 (IL-2). In the BME group, mitogen-activated protein kinase 1 (MAPK1) expression increased, whilst expression of signal transducer and activator of transcription 3 (STAT3) decreased. Additionally, matrix metalloproteinase-9 (MMP9) expression decreased.

CONCLUSIONS

The results of this study indicate that BME significantly induced pulmonary function injury leading to emphysema and bronchiectasis changes, as well as systemic inflammation. IL-10 may play a significant role in the pro-inflammatory/anti-inflammatory mechanisms of COPD by regulating the expression of key signalling pathway proteins. A novel COPD modeling method incorporating elastase was constructed.