Abstract: Objective To investigate the protective mechanism of histone deacetylase inhibitor ACY1215 on liver mitochondrial damage in rats with acute hepatic failure（AHF）. Methods 24 male SD rats were randomly divided into control group,model group and ACY1215-intervened group. Lipopolysaccharide（LPS） and D-galactosamine （D-Gal） were used to establish acute liver failure model in rats. The ACY1215 （10 mg·kg-1） was given 2 hours before the establishment of acute liver failure. Serum and liver samples of rats were obtained at end of 48 hours after AHF induction. The liver histological changes were observed by light and electron microscopy,and the mitochondria of hepatocytes were separated by gradient centrifugation. The relative fluorescence （RFU） of mitochondrial membrane permeability transition porosity （MPTP） was tested by fluorescence spectrometry. The content of cytochrome C（Cytc） in mitochondria supernatants was determined by ELISA. The contents of serum ALT,AST and total bilirubin were detected by routine biochemical method. Results Compared with in the model group,the degree of liver histological damage was reduced in the ACY1215-intervened group,and the mitochondrial swelling of the hepatocytes was improved;serum ALT [（5114.1±252.6） U/L vs. （56.0±4.4） U/L],AST [（2909.8±31.7） U/L vs. （130.4±12.6） U/L] and total bilirubin levels [（97.6±1.4） μmol/L vs. （7.4±0.7） μmol/L] in the model group were significantly higher than those in the control group （P<0.05）,while they[（799.4±11.2） U/L,（401.0±5.6） U/L and（28.0±1.2） μmol/L,respectively] in the ACY1215-intervened group significantly decreases as compared to those in the model group（P<0.05）;the MPTP in acute liver failure model group was significantly higher than that in the normal control group[（968220.0±16733.1） RFU/mgprot vs.（156300.0±24043.3）RFU/mgprot，P<0.05）]，and also higher than in the ACY1215-intervened group [（127150.0±12337.6） RFU/mgprot，P<0.05]；the mitochondrial Cytc level in the model group was significantly lower than that in the control group [（0.17±0.03） ng/mgprot vs. （0.39±0.10） ng/mgprot，P<0.05]，and also lower than that in the ACY1215-intervened group [（0.32±0.06） ng/mgprot，P<0.05]. Conclusion ACY1215 has a protective effect on liver mitochondria in rats with acute hepatic failure，and the mechanism might be the inhibition of opening of mitochondrial MPTP in the livers and reduction of translocation of Cytc into the cytoplasm.

Key words: Acute hepatic failure, Mitochondria, Histone deacetylase inhibitor ACY1215, Rats