Abstract

Introduction: Glycyrrhizin (GL) was recently found to suppress the HMGB1-induced injury by binding directly to it. However, the effect of GL on HMGB1 expression in endotoxemia as well as its underlying molecular mechanism remained unclear

Methods: Twenty-one pigs were divided into four groups: Sham group (n=3), Control group (n=6), Ethyl pyruvate group(n=6) and Glycyrrhizin group(n=6). Pigs were anesthetized, mechanically ventilated, monitored and received a continuous intravenous infusion of lipopolysaccharide (LPS). Twelve hours after the start of the LPS infusion, ethyl pyruvate (30 mg•kg-1•hr-1) or glycyrrhizin (1 mg•kg-1•hr-1) was administered for 12 hrs. Measurements of systemic and pulmonary hemodynamics, oxygen exchange, and metabolic status were performed. The concentrations of cytokines in serum and the corresponding gene and protein expressions in tissue samples from liver, lungs, kidneys, small  intestine and lymph nodes were measured. 

Results: GL could maintain the stability of systemic hemodynamics, improve pulmonary oxygen exchange and metabolic status. GL could attenuate organ injury and decrease the serum levels of HMGB1 and other pro-inflammatory cytokines through inhibiting their gene and protein expression

Conclusions:  GL could improve systemic hemodynamics and protect vital organs against porcine endotoxemia through modulation of systemic inflammatory response. By reducing serum level and gene expression of HMGB1 and other pro-inflammatory  cytokines, GL might become a potential agent for the treatment of sepsis.