Egr-1在大鼠酒精性脂肪肝中的表达及水飞蓟素对其干预作用

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。

Expression of Egr-1 and the effects of silymarin on alcoholic fatty liver in rat

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-1）,and high dose of group（200 mg·kg-1）.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 aminotransferase（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（P0.01）.The activities of serum ALT and AST were significantly increased in the model group compared with the normal group（P0.01,P0.05）.Compared with model group,high dose of silymarin group could significantly reduce the degree of pathological changes in liver tissue（P0.01）.Immunohistochemistry showed that the expression of Egr-1 and TNF-α in model group was markedly higher than those in normal group（P0.01）,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（P0.01,P0.05）.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（P0.05）,and high dose of silymarin could significantly reduce the expression of Egr-1 compared with model group（P0.05）.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.