表没食子儿茶素没食子酸酯对酒精性肝病小鼠肝脏Tf和TfR1表达的影响

Effects of Epigallocatechin-3-gallate on Expression of Tf and TfR1 in Liver of Mice with Alcoholic Liver Disease

摘要:

目的: 探讨表没食子儿茶素没食子酸酯(EGCG)对酒精性肝病(ALD)小鼠肝脏转铁蛋白(Tf)、转铁蛋白受体1(TfR1)表达的影响。 方法: 6~8 周龄雄性无特定病原体(SPF)级C57/BL6小鼠随机分为正常组和模型组,模型组小鼠每日予乙醇灌胃,并于造模第9周随机分为模型组,EGCG 10,20,30 mg·kg^-1组。给药4 周后处死小鼠,观察各组小鼠肝脏病理变化,并测定肝功能、肝肝铁含量,采用蛋白免疫印迹法检测肝组织Tf,TfR1的表达。 结果: 模型组小鼠与正常对照组相比血清谷丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平显著升高(P<0.01), 肝组织病理表现肝细胞呈中度脂肪变性,肝铁含量及肝脏 Tf,TfR1表达显著升高(P<0.01)。EGCG治疗组显著降低血清 ALT,AST 水平(P<0.01),肝组织病理变化可见显著改善,肝铁含量及肝脏Tf,TfR1表达显著降低(P<0.01)。 结论: EGCG可以降低ALD小鼠肝脏Tf,TfR1的表达水平,抑制肝铁摄取,从而发挥其对酒精性肝病的保护作用。

Abstract:

Objective:To study the effects of epigallocatechin-3-gallate(EGCG)on transferrin(Tf)in liver of mice with alcoholic liver disease(ALD) and to explore its mechanisms. Method: C57/BL6 mice were randomly divided into two groups: normal group and model group. Alcoholic liver disease was induced by gavage of alcohol for 12 weeks. At the end of 8 weeks, the alcohol group was divided into four subgroups: model group, EGCG (20 mg·kg^-1) group, EGCG (10 mg·kg^-1) group, EGCG (30 mg·kg^-1) group. Mice in the EGCG groups were received an intraperitoneal injection of EGCG via simultaneous intragastric administration with normal saline or alcohol for 4 weeks. Liver injuries were assessed by histopathologic examination and serum alanine aminotransferase(ALT), aspartate aminotransferase(AST)levels. In addition, liver iron levels and Tf, transferin receptor 1(TfR1)of liver tissue were evaluated. Result: Model group mice had marked increase in serum ALT, AST levels and liver iron concentration compared with normal group, and their liver tissues showed moderate hepatocytes fatty degeneration. However, every treatments groups resulted in decreased ALT, AST levels and liver iron concentration and improved pathological changes. Liver Tf and TfR1 protein expression levels were elevated significantly in model group compared with normal group, but markedly suppressed by EGCG treatments. Conclusion: Compared with model group, treatment of ALD mice with EGCG decreased Tf and TfR1 protein expression in the liver. EGCG might play a protective role in the development of ALD. This beneficial effect of EGCG may be attributed to its iron chelation ability. The possible mechanisms is that EGCG decreases the hepatic iron uptake by the downregulation of Tf and TfR1.