Protective effects of ketamine combined with ulinastatin against endotoxin induced acute lung injury in rats

Abstract

Objective To investigate the effects of ketamine combined with ulinastatin against endotoxin-induced acute lung injury (ALI) in rats Methods One hundred healthy male SD rats,weight 208 g-320 g,were randomly divided into 5 groups equally:group I normal control ( C ) ; group Ⅱ endotoxin (L) ; group Ⅲ ketamine ( K ) ; group Ⅳ ulinastatin (U) and group Ⅴ ( K+U).The animals received 2 doses of lipopolysaccharide (LPS) (intraperitoneal LPS 1 mg/kg and iv LPS 1.5 mg/kg) at 16 h interval in group Ⅱ togroupⅤ.The animals received ulinastatin 50 000 U/kg iv after second dose of LPS in group U and K+U.Ketamine was infused iv at 10 mg·kg-1·h-1 in group K and K+U.Five animals in each group were killed by exsanguination at 1,2,3 and 4 h after second LPS administration.W/D lung weight ratio,blood gases,serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 concentrations and nuclear factor-κB (NF-κB) activity and inhibitor of nuclear factor κBα (IκBα) protein expression in the lung tissue were determined. Results LPS administration significantly increased serum TNF-α and IL-6 concentration and NF-κB activity in the lung tissue and decreased IκBα protein expression in group Ⅱ as compared with control group.The LPS-induced changes were attenuated by K/U/K+U in group Ⅲ, Ⅳ and Ⅴ. Compared with group K or group U,serum TNF -αand IL-6 concentration and NF-κB activity (2.49±0.23) in the lung tissue decreased,IκBα protein expression (35.1±3.4) increased significantly,and W/D lung weight ratio (4.91±0.16) and lung pathologic score (7.8±0.8) were lower in group K+U.Conclusions Ketamine and ulinastatin have protective effects against LPS induced acute lung injury by inhibiting NF-κB activity,neutrophil activation and inflammatory responses,and are synergistic. Key words: Ketamine; Ulinastatin; Endotoxemia; Respiratory distress syndrome