Abstract:

Objective  To investigate the relationship between nuclear factor(NF)-κB signaling pathway and gender differences in alcoholic liver fibrosis.    Methods  C57BL/6 N mice at 7-8 weeks of age were randomly divided into: male normal group, male model group, female normal group and female model group of 20 mice each. The normal group was fed with control liquid diet for 8 weeks, and the model group was fed with alcoholic liquid diet for 8 weeks combined with 31.5% ethanol gavage (5g/kg twice a week) to establish an alcoholic liver fibrosis model. The mice were executed at the end of 8 weekends, and the alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity, estradiol (E₂) and testosterone (T) levels were detected in each group, and the fibrosis was detected in each group by Sirius red staining, and liver histopathological changes were observed by HE staining. The postive area rate of NF-κB-P65 and α-SMA were detected by immunohistochemistry and the expression levels of collagen Ⅰ, tumor necrosis factor-α(TNF-α),phosphorylated nuclear factor κB-P65(p-NF-κB-P65), inhibitor of NF-κB(IκBα), and phosphorylated IκBα(p-IκBα) were detected by wes Western blotting.   Results  The male model group showed increased levels of ALT, AST enzyme activity and T, decreased levels of E₂, increased collagen fibrils, increased HE staining necrosis score, increased positive area rate of NF-κB-P65 and α-smooth muscle actin(α-SMA), increased expression of collagen Ⅰ, TNF-α, p-NF-κB-P65, p-IκBα and decreased expression of IκBα.   Conclusion  Alcohol is more likely to cause liver fibrosis in male mice, which may be related to enhanced IκBα phosphorylation releasing NF-κB, contributing to increased phosphorylated NF-κB-P65 and further activation of NF-κB signaling pathway.

Key words: Alcoholic liver fibrosis, Nuclear factor-κB signaling pathway, Gender differences, Western blotting, Mouse