RESUMO
Melatonin (MT) is an indoleamine hormone that can counteract ischemiainduced organ injury through its antioxidant effects. The aim of the present study was to investigate the protective effects of exogenous MT against hemorrhagic shock (HS)induced hepatic ischemic injury in rats, and the role of the nuclear factor (NF)κB signaling pathway in this process. A rat model of HSinduced hepatic ischemic injury was established. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), glutamate dehydrogenase (GDH), tumor necrosis factor (TNF)α, interferon (IFN)γ, interleukin (IL)6 and IL1ß were measured every 6 h, and the 24h survival rate of the rats was analyzed. All surviving rats were sacrificed after 24 h. Pathological changes in the liver and the hepatocyte apoptosis rate were observed by hematoxylin and eosin staining and TUNEL assay, respectively, and the expression levels of NFκB p65 and NFκB inhibitor α (IκBα) were analyzed by reverse transcriptionquantitative PCR analysis and western blotting. The results demonstrated that the serum levels of ALT, AST, LDH, GDH, TNFα, IFNγ, IL6 and IL1ß gradually increased after HS compared with those in rats subjected to a sham procedure, but this increase was attenuated by MT. Furthermore, the survival rate of the MT group was significantly higher compared with that of the HS group. The degree of pathological hepatic injury, the hepatocyte apoptosis rate, and the hepatic levels of TNFα, IFNγ, IL6 and IL1ß were significantly decreased in the MT group compared with the HS group. In addition, the mRNA expression of NFκB p65 was significantly decreased and the mRNA expression of IκBα was significantly increased in the MT group compared with the sham group. Furthermore, the NFκB p65 protein levels in the MT group were significantly increased in the cytosol but decreased in the nucleus, and the IκBα protein levels were increased while those of phosphorylated IκBα were decreased compared with those in the HS group. Therefore, it may be inferred that exogenous MT alleviates HSinduced hepatic ischemic injury in rats via the inhibition of NFκB activation and IκBα phosphorylation.