This study was aimed to observe effects of different doses of D-galactosamine (D-GalN) plus lipopoly-saccharide (LPS) and blood coagulation changes among rat model of acute liver failure, in order to establish an ideal model of acute liver failure in rats. SD rats were randomly divided into the control group, D-GalN high, medium and low dose groups, with 10 rats in each group. Except the normal group, rats in other groups were injected with D-GalN plus LPS at different doses to induce acute liver failure. The mortality of rats was observed. The liver function and blood coagulation were detected from rat serum at 0 h, 12 h, 24 h, 48 h, and 72 h. HE stain was used in the observa-tion of changes on liver pathological changes. The results showed that the mortality of D-GalN high, medium and low dose groups within 72 h were 60%, 30%, 10%, respectively. There were significant differences on the serum content level of ALT, AST, TBIL, PT, INR, FIB from different dose groups at different time points and the normal group (P<0.05). However, the comparison among D-GalN high, medium and low dose groups showed no statistical difference on ALT and AST; while there were statistical differences on TBIL, PT, INR and FIB (P < 0.05). It was concluded that coagulation index was more stable in the liver failure model. Through observation on the liver function, blood coagulation and pathological morphology, the model of acute liver failure induced with medium dose of D-GalN plus LPS in SD rats at 48 h was more similar to the clinical symptom of acute liver failure. Therefore, the medium dose was the ideal model inducing dose.

OBJECTIVETo observe the effects of Sanhuangyinchi decoction (SHYCD) pretreatment on acute hepatic failure (AHF) induced by D-galactosamine and lipopolysaccharide (LPS) in rats and explore the possible mechanisms involving antioxidant stress and cell apoptosis-related protein expression.

METHODSForty-eight SD rats were randomized equally into control group, AHF model group, high-, medium- and low-dose SHYCD groups, and Bicyclol group. Five days after administration of the corresponding drugs, the rats were challenged with peritoneal D-galactosamine (700 mg/kg) plus LPS (10 ug/kg) injections to induce AHF acute hepatic failure except for those in the control group. At 48 h after the injections, blood samples were collected from the rats to detect the levels of ALT, AST, TBIL, PT, INR and FIB, and pathological changes and superoxide dismutase (SOD) and malondialdehyde (MDA) contents in the liver were examined; immunohistochemistry and western blotting were used to detect caspase-3 protein expression in the liver.

RESULTSThe levels of ALT, AST, TBIL, TP and INR in the 3 SHYCD groups and Bicyclol group significantly decreased (P<0.05) while FIB significantly increased in comparison with those in the model group. SHYCD obviously ameliorated the pathological changes, enhanced SOD activity (P<0.05), and decreased MDA levels (P<0.05) and caspase-3 expression (P<0.05) in the liver tissue. SHYCD at the medium dose produced similar effects to Bicyclol (P>0.05) and showed better effects at the high dose than Bicyclol (P<0.05).

CONCLUSIONSHYCD pretreatment can dose-dependently ameliorate AHF in rats possibly by suppressing antioxidant stress and caspase-3 expression to decrease hepatic cell apoptosis.

Animals ; Caspase 3 ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Liver Failure, Acute ; drug therapy ; metabolism ; prevention & control ; Male ; Malondialdehyde ; metabolism ; Oxidative Stress ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism