Abstract:

Objective To investigate the relationships among the chronic alcohol exposure, stress injury of liver-brain and ceramide’s effect. Methods The chronic alcohol exposure models in both wide type (WT) and sphingomyelin synthetase 2 knockout (SMS2-/-) mice were established. HE staining, Masson staining, c-Fos and NF-κB immunolabeling, Western blotting analysis and trranssmission electron microscopy were carried out. Results Alcohol exposure led to the wild-type and SMS₂^-/- mice hepatocytic steatosis and hepatic fibrosis. Mallory bodies and inflammatory cell infiltration were found in liver. After alcohol exposure, c-Fos and NF-κB positive cells increased in hippocampal CA1 area with dose dependency (P<0.01). However, comparing with the WT pups, the number of positive c-Fos and NF-κB cells in SMS₂^-/- mice increased much more than WT mice (P<0.05). Immunoblotting evidence of c-Fos and NF-κB protein supported the data of immunohistochemistry in both in WT and SMS₂^-/-mice (P<0.01 )Conclusion Oxidative stress and inflammatory responses in liver and CNS are the main pathological alterations after chronic alcohol exposure. The alcoholinducing oxidative stress probably is the cause of insulin resistance in organism. Ceramide is involved in the processes above through c-Fos and NF-κB pathway. Alcohol exposure induces the oxidative stress injury in liverbrain axis, such as inflammatory responses and the expression of oxidative stress cues, c-Fos and NF-κB. Ceramide increases the alterations above.