The protective effect of ulinastatin on GalN/LPS-induced acute liver injury in rats

Objective To study the effect of ulinastatin (UTI) on GalN/LPS-induced acute liver injury in rats and to investigate its mechanism of action. Methods Seventy-two male SD rats were randomly divided into normal control group,model group and UTI treatment group. Every group was divided into four subgroups:6,12,24,and 48 hours groups with 6 rats in each group. Acute liver injury were induced in the model group and UTI treatment group rats by intraperitoneal injection of D-galactosamine (D-GalN) and lipopolysaccharide (LPS). After model establishment,UTI was immediately administered by intraperitoneal injections in the UTI treatment group. Blood samples were collected from the portal vein to detect the contents of serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),tumor necrosis factor (TNF)-α,nitric oxide (NO). Livers were dissected for measurements of Caspase-3 activity,Caspase-8 activity,MDA content,and histological changes. Results UTI significantly attenuated GalN/LPS-induced increase in serum ALT,AST activity and TNF-α,as well as NO concentration. Compared with model group,the levels of ALT and AST in UTI treatment group had statistical significance at 12,24,and 48 hours (P0.01). The levels of TNF-α and NO in UTI treatment group had statistical significance at 6 and 12 hours (P0.01 or 0.05). Compared with model group,Caspase-3 activity and Caspase-8 activity in UTI treatment group were decreased obviously at 6 hours (P0.01),and the levels of MDA in UTI treatment group were decreased obviously at 12,24,48 hours (P0.01). Conclusion UTI attenuates GalN/LPS-induced acute liver injury via its anti-inflammatory,anti-oxidant,and anti-apoptotic effects.