Effects of Ulinastatin on Caspase-3,Caspase-8 and Bcl-2 in GalN/LPS-induced Acute Liver Failure in Rats

Objective To study the effect of ulinastatin on Caspase-3,Caspase-8 and Bcl-2 in GalN/LPS-induced acute liver failure's in rats.To understand the relationship between the hepatocyte apoptosis and acute liver failure,and their correlation with prognosis in acute liver failure's rat treated by ulinastatin.Methods There were 96 male SD rats were randomly divided into 3 groups: normal control group,model group,UTI treatment group.Model group and UTI treatment group were divided into fives subgroups: 6,12,24,36 and 48 hours groups with 6 rats in each group.The survival rates of 15 ALF rats which were taken from every group were observed.The model group and UTI treatment group rats induced acute liver injury model by intraperitoneal injections D-galactosamine(D-GalN) and lipopolysaccharide(LPS).After model established,UTI was administered by intraperitoneal injections immediately in the UTI treatment group and 0.4mL 0.9% natrium chloride was administered by intraperitoneal injections immediately in the model group.At the same time,2mL 0.9%natrium chloride was administered by intraperitoneal injections in the normal control group.Plasma ALT,AST etc.were detected,The contents of serum tumor necrosis factor-α(TNF)-α was detected by ELISA.We observed the pathological characters of liver tissue under common microscope after hematoxylin-eosin staining.And the expression of Bcl-2 in liver tissue was detected by S-P immunohistochemical staining.Other liver's tissues were dissected for measurements of Caspase-3 activity,Caspase-8 activity.Results Compared with model group,the survival rates and the expression of Bcl-2 protein in UTI treatment group were increased obviously,the level of ALT,AST,TNF-α were decreased,Caspase-3 activity and Caspase-8 activity,were decreased.Conclusion Ulinastatin is efficient to improve the survival rate,its action mechanisms are probably involved in the inhibition of inflammatory factor production,just as TNF-α,and suppression of Caspase-3 and Caspase-8 expression.In addition,Ulinastatin attenuates GalN/LPS-induced acute liver failure via its improvement on the expression of Bcl-2 protein.