Protective effects of Nod-like receptor protein-3 inflammasome inhibitor glyburide for mouse acute lung injury induced by mechanical ventilation

Abstract

Objective To investigate whether Nod-like receptor protein-3(NLRP3) inflammasome inhibitor glyburide exerts protective effects for mouse acute lung injury induced by mechanical ventilation. Methods Twenty-eight male ICR mice were randomly divided into 4 groups: control group(group CON, n=6), glyburide group(group GLY, n=6), mechanical ventilation group (group VEN, n=8), and glyburide+mechanical ventilation group(group GLY+VEN, n=8). The content of protein and inflammatory cell counts in bronchoalveolar lavage fluid were measured after 4 h ventilation, the wet/dry(W/D) and morphopathogical changes of lung tissue were examined. Lung tissues were homogenated to detect the IL-1β, IL-6 and TNF-α levels by ELISA. Results The concentration of protein and cell counts in group VEN[(0.534±0.104) g/L and (3.4±0.7) ×105/ml] were higher than group CON[(0.167±0.021) g/L and (1.86±0.46) ×105/ml](P<0.01), and those in group GLY+VEN[(0.425±0.083) g/L and (2.4±0.6) ×105/ml] were lower than group VEN(P<0.05). W/D was higher in group VEN(5.1±0.5) than group CON(4.4±0.4)(P<0.01) and group GLY+VEN(4.7±0.4)(P<0.05). The IL-1β, IL-6 and TNF-α levels in lung tissue were increased in group VEN and group GLY+VEN(P<0.05). The IL-1β and IL-6 levels had significant statistical differences between group GLY+VEN and group VEN(P<0.05). Conclusions Our results indicate that pre-treated with glyburide could significantly attenuate mechanical ventilation-induced recruitment of inflammatory cells and lung edema, which might be attributed to the deactivation of NLRP3 inflammasome. Key words: Mechanical ventilation; Acute lung injury; Glyburide; Pro-inflammatory cytokines; Nod-like receptor protein-3 inflammasome