P22077

Inhibitory Effect of P22077 on Airway Inflammation in Rats with COPD and Its Mechanism

Purpose:
This study investigated the pharmacological effects of P22077 on airway inflammation triggered by lipopolysaccharide and cigarette smoke, aiming to explore its therapeutic mechanism in a rat model of chronic obstructive pulmonary disease (COPD).

Patients and Methods:
The COPD model was established using lipopolysaccharide exposure combined with smoke fumigation. Animals were treated with either a vehicle control or P22077. Serum, bronchoalveolar lavage fluid (BALF), and lung tissues were collected for further analysis.

Results:
P22077 treatment significantly alleviated airway inflammation in COPD rats by reducing leukocyte infiltration in BALF and decreasing hypersecretion of interleukin-18 (IL-18) and interleukin-1β (IL-1β) in both BALF and serum. Hematoxylin and eosin (H&E) staining demonstrated that P22077 mitigated emphysema, immune cell infiltration, and airway wall damage. Periodic acid–Schiff (PAS) staining revealed a marked reduction in the proliferation of goblet cells in the airway walls and fewer bronchial goblet cells in rats treated with P22077. Additionally, P22077 inhibited the formation of the NLRP3/ASC/Caspase-1 inflammasome complex, suppressing the inflammatory response driven by IL-1β and IL-18.

Conclusion:
P22077 effectively downregulates NLRP3 inflammasome signaling, reducing the expression of associated inflammatory proteins and factors. This leads to decreased airway inflammation and reduced aggregation of inflammatory cells in COPD rats, suggesting that its therapeutic effect may be linked to suppression of the NLRP3 pathway.