目的 研究Egr-1在大鼠酒精性脂肪肝中的表达,观察水飞蓟素对酒精性脂肪肝肝组织中Egr-1表达的影响.方法 55只大鼠随机分为4组:正常组、模型组、水飞蓟素低剂量组(100 mg· kg-1)、水飞蓟素高剂量组(200 mg· kg-1),采用高脂饮食联合酒精灌胃6周建立大鼠酒精性脂肪肝模型.全自动生化分析仪检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)的活性;HE染色观察肝脏病理学变化;免疫组织化学法检测肝脏Egr-1,TNF-α的表达;蛋白免疫印迹(Western Blot)法检测肝脏Egr-1的表达情况.结果 与正常组比较,模型组肝细胞可见明显脂肪变性,肝细胞肿胀明显(P<0.01),血清中ALT、AST活性明显升高(P<0.01,P<0.05),与模型组比较,水飞蓟素高剂量组肝组织病理变化程度明显减轻(P<0.01),血清ALT、AST活性明显降低(P<0.05);免疫组化结果显示,Egr-1、TNF-α在模型组表达较正常组明显升高(P<0.01),而在水飞蓟素高剂量组(200 mg·kg-1)明显减少(P<0.01,P<0.05);Western Blot结果显示,模型组肝组织中Egr-1的表达量明显高于正常组(P<0.05),而水飞蓟素高剂量组较模型组Egr-1的表达明显减少(P<0.05).结论 Egr-1在酒精性脂肪肝大鼠肝组织中表达明显升高,可能参与了酒精性脂肪肝的发病机制.水飞蓟素对酒精性脂肪肝具有一定的保护作用,其保护机制可能部分地与抑制Egr-1的活化,进而减少TNF-α的形成有关.%Objective To investigate the expression of Egr-1 in rat alcoholic fatty liver and the effects of Silymarin on the expression of Egr-1 in hepatic tissue of alcoholic fatty liver rats. Methods Fifty-five rats were randomly divided into four groups: normal control group,model control group,low dose of silymarin group( 100 mg · kg~ ),and high dose of group( 200 mg · kg~ ). Rat model of alcoholic fatty liver was induced by intragastric infusion of ethanol and high-fat diet for six weeks. The activities of serum alanine aminotrans-ferase( ALT )and aspartate aminotransferase( AST )were measured by routine laboratory methods using an autoanalyzer. Histopathological changes of liver were assessed by hematoxylin and eosin( HE )staining. The expression of Egr-1 was determined by immunohistochemical and Western Blot. The expression of TNF-α in liver tissue was measured by immunohistochemical. Results Compared with normal group,the liver cells of model group showed obvious steatosis and significant swelling( P<0.01 ). The activities of serum ALT and AST were significantly increased in the model group compared with the normal group( P <0. 01 ,P <0. 05 ). Compared with model group,high dose of silymarin group could significantly reduce the degree of pathological changes in liver tissue( P <0. 01 ). Immunohistochemistry showed that the expression of Egr-1 and TNF-α in 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( 200 mg · kg -1 )could significantly decrease the expression of Egr-1 and TNF-α( P <0. 01 ,P <0. 05 ). Western Blot showed that the expression of Egr-1 of the model group in the liver tissue was significantly higher than that in normal group( P < 0. 05 ), and high dose of silymarin could significantly reduce the expression of Egr-1 compared with model group( P <0. 05 ). Conclusions The expression of Egr-1 is significantly increased in rat alcoholic fatty liver, and it may be involved in the pathogenesis of alcoholic fatty liver. Silymarin has 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-α.
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