[Therapeutic effects of emodin on acute cholestatic hepatitis and mechanism thereof: experiment with rats].

Objective To investigate the therapeutic effects of emodin on acute cholestatic hepatitis and mechanism thereof. Methods 96 SD rats were randomly divided into 4 groups to be treated with emodin, ursodeoxycholic acid, dexamethasone, or normal saline respectively for 4 days. On the 5th day gastric perfusion of alpha-naphthylisothiocyanate (ANIT) was performed to establish models of cholestatic hepatitis. 4-6 hours after the establishment of model the above mentioned agents were given continuously. 24, 48, and 72 hours after the model establishment blood samples were collected from abdominal aorta to examine the total bilirubin (TB), direct bilirubin (DB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyhransferase (GGT), and total bile acid (TBA). Specimen of liver was collected to undergo pathological examination. PCR was used to detect the mRNA expression of cytokine-induced neutrophil chemoattractant 1 (CINC-I) and macrophage inflammatory protein 2 (MIP-2), and Western blotting was used to detect the protein expression of intercellular adhesion molecule 1 (ICAM-1) . Twenty-four rats treated with NS only were used as controls. Results The pathological changes of behaviors and liver of the emodin and ursodeoxycholic acid groups were all remarkably milder than those of other model groups. The levels of TB [(32.8±3.7) μmol/L, (61.0±16.4) μmol/L, (10.8±4.5) μmol/L], DB[(26.03±3.10) μmol/L, (49.40±18.16)μmol/L, (8.04±3.03) μmol/L], and ALT [(314±50) U/L, (664±97)U/L, (200±60) U/L], at the time points 24, 48, and 72 hours, the 48 and 72 hours AST levels, the 48 hours ALP level, the 72 hours GGT level, and the 48 and 72 hours TBA levels of the emodin group were all significantly lower than those of the model group (all P<0.05). The 24 and 48 hours TB levels, 24 hours DB and ALT,and 24,72 hours TBA levels of the emodin group were all significantly lower than those of the ursodeoxycholic acid group (all P<0.05). The 24,48 hours TB and TBA levels, and the ALT,AST and GGT levels at all time points of the emodin group were all significantly lower than those of the dexamethasone group (all P<0.05). The CINC-1 and MIP-2 mRNA expression levels and ICAM-1 protein expression levels at all time points of the emodin group were all significantly lower than those of the model group (all P<0.05). Conclusion Decreasing the levels of TB, DB and ALT in particular, emodin has a protective effect on cholestatic hepatitis. Its effects are quicker than ursodeoxycholic acid, and it has better effects on ALT, AST GGT, and TBA than dexamethasone . These effects may be due to inhibition of the activation of CINC-1, MIP-2, and ICAM-1. Key words: Emodin;  Hepatitis,animal;  Chemokines;  Cell adhesion molecules