Dexmedetomidine attenuates acute alcoholic hepatic injury in mice / 中国病理生理杂志

ABSTRACT

AIM:To investigate the effects of dexmedetomidine (DEX) on acute alcoholic hepatic injury in mice and to explore the possible mechanisms .METHODS:Kunming mice (n=50) were randomly divided into 5 groups (n=10)normal saline control (NS) group, acute alcoholic hepatic injury model (E) group, low-dose (10μg/kg) DEX (E+L) group, medium-dose (50 μg/kg) DEX (E+M) group and high-dose (100 μg/kg) DEX (E+H) group.The animals were sacrificed at 6 h after gavage of alcohol or normal saline .The levels of alanine aminotransferase ( ALT) , as-partate aminotransferase (AST), triglyceride (TG), malondialdehyde (MDA), glutathione (GSH) and superoxide dis-mutase ( SOD) were measured .The livers were removed for evaluation of histological characteristics and determining the content of tumor necrosis factor-α( TNF-α) amd interleukin-1β( IL-1β) in the liver tissues by ELISA .The expression levels of cytochrome P4502E1 (CYP2E1) and nuclear factor -κB (NF-κB) in the liver tissues were evaluated by Western blot.RESULTS:Compared with NS group, the levels of ALT, AST and TG were obviously increased in E group , which were obviously decreased in E +M and E+H groups.Compared with NS group, the levels of TNF-α, IL-1βand MDA were obviously increase in E group , which were obviously decreased in E +M and E+H groups.Compared with NS group, the activity of SOD and the content of GSH were obviously decreased in E group , which were obviously increased in E +M and E+H groups.Compared with NS group, the expression of CYP2E1 and NF-κB was obviously increase in E group , which was obviously decreased in E +M and E+H groups.Compared with NS group , ethanol induced marked liver histo- logical injury, which was less pronounced in E +M and E+H groups.CONCLUSION: DEX has a protective effect on mouse liver with acute alcoholic injury by the involvement in the processes of antioxidation and antiinflammation , and its mechanism may be associated with the inhibition of CYP 2E1 and NF-κB expression.