| Background The pathogenesis of alcoholic fatty liver has not been fully elucidated yet. In recent years, studies have found that pro-inflammatory transcription factor and inflammatory factor appear to involve in alcoholic fatty liver pathological damage process and play an important role in the occurrence and development of the alcoholic fatty liver. Early growth response factor-1which is an important factor promoting pro-inflammatory nuclear transcription factor is considered to be one of the key factors of early inflammation priming. In recent years, the study also found that Egr-1has the dual role in liver damage. On the one hand, it has protective effect, on the other hand it can start early inflammatory reaction by raising the expression of tumor necrosis factor-alpha(TNF alpha). Egr-1involves in the process of early inflammatory reactions in alcoholic fatty liver. Its mechanism is unclear, and it may raise the expression of TNF-a, and then cause inflammation reaction. Silymarin which is a safe,stable and effective liver protective drugs has a strong antioxidant effect. Therefore, our study clarified the effects of Egr-1in pathogenesis of alcoholic fatty liver by establishing the model of alcoholic fatty liver, and to explore whether the protective effect of Silymarin on alcoholic fatty liver relates to inhibit the expression of Egr-1.Objective To investigate the expression of Egr-1in pathogenesis of alcoholic fatty liver, and to explore whether the protective effect of Silymarin on alcoholic fatty liver relates to inhibiting the expression of Egr-1. Methods Fifty-five rats were randomly divided into four groups:normal control group, model control group, low dose of silymarin group(100mg/kg), and high dose of group (200mg/kg). Rat model of alcoholic fatty liver was induced by intragastric infusion of ethanol and high-fat diet for six weeks. The activities of alanine transarninase(ALT) and aspartate aminotransferase(AST), the levels of total bilirubin(TBIL),total cholesterol(TC) and triglyceride(TG) in serum were detected with routine laboratory methods using an autoanalyzer. Histopathological changes of liver were assessed by hematoxylin and eosin (HE) staining. The TG content in liver tissue was determined by spectrophotometry. The expression of Egr-1was determined by immunohistochemical and Western Blot. The expression of TNF-a and IL-6in liver tissue was measured by immunohistochemical.Results Compared with normal group, the liver cells of model group showed significantly swelling and visible fat vacuoles of various sizes, lipid droplets, inflammatory cells infiltration, Mallory small body and dot, focal necrosis and degeneration (P<0.01).The activities of AST and ALT were increased in model group(P<0.05and P<0.01,respectively) compared with normal control group. The levels of TBIL and TG were significantly higher in model group than those in normal control group(P<0.05and P<0.01,respectively).Compared with model group, high dose of silymarin group can significantly reduce the degree of pathological changes in liver tissue(P<0.01).The level of TG was significantly higher in model group than that in normal control group(P<0.01). Immunohistochemistry showed that the expression of Egr-1, TNF-a and IL-6in model group was markedly higher than those in normal group (P<0.01),while in comparison with model group, treatment with high dose of silymarin (200mg/kg) could significantly decrease the expression of Egr-1, TNF-a and IL-6(P<0.01,P<0.05). Western Blot showed that the expression of Egr-1of the model group in the liver tissue was significantly higher than that in normal group(P<0.05), and high dose of silymarin can significantly reduce the expression of Egr-1compared with model group(P<0.05).Conclusion The expression of Egr-1was significantly increased in rat alcoholic fatty liver, and it may be involved in the pathogenesis of alcoholic fatty liver. Silymarin had a certain protective effect in alcoholic fatty liver and the protective effect may be related to inhibiting the activation of Egr-1, thereby reducing the formation of TNF-a. |
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