Dulaglutide provides protection against sepsis-induced lung injury in mice by inhibiting inflammation and apoptosis

Sepsis is a dangerous condition with a high mortality rate. In addition to promoting insulin secretion in a glucose -dependent manner, glucagon-like peptide-1 (GLP-1) also exhibits anti-inflammatory properties. Dulaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA). In this study, we investigated the effects and mechanism of action of dulaglutide (Dul) in lipopolysaccharide (LPS) induced lung injury in mice with sepsis. In mice with LPS (15 mg/kg, ip, qd)-induced acute lung injury, the administration of dulaglutide (0.6 mg/kg, ip, qd) improved weight loss, reduced lung injury, reversed the increase in IL-1 beta, TNF-alpha, IL-6, CXCL1, CCL2 and CXCL2 expression in the lung, and reduced the infiltration of neutrophils and macrophages in the lung tissues. The decline in caspase-3, cleaved caspase-3, caspase-8, and Bcl-2/Bax expression and the increase in the number of TUNEL positive cells in the lung were reversed, suggesting that GLP-1RA could play a protective role in the lung by inhibiting inflammation and apoptosis. In addition, GLP-1RA could reduce the expression of P-STAT3 and NLRP3, suggesting that P-STAT3 and NLRP3 may be potential targets against lung injury in sepsis. Collectively, our data demonstrated that GLP-1RA exerts a protective effect against sepsis-induced lung injury through mechanisms related to the inhibition of inflammation, apoptosis, and STAT3 signaling.

Automated summary

This study investigated the effects and mechanism of action of dulaglutide in lipopolysaccharide-induced lung injury in mice with sepsis. The results showed that dulaglutide improved weight loss, reduced lung injury, reversed the increase in inflammatory cytokine expression, and reduced the infiltration of immune cells in the lung tissues. Additionally, dulaglutide reduced the expression of STAT3 and NLRP3, suggesting their potential as therapeutic targets for sepsis-induced lung injury.