补锌对小鼠酒精性肝病的作用及对HNF-4α的影响  

Effect of dietary zinc supplement on liver regeneration in mice with alcoholic liver disease and its relation to hepatocyte nuclear factor-4 α

作　　者：肖敏[1] 李军伟[2] 孙未 董缪武[3] 陈锡文[1] 

机构地区：[1]温州医学院实验动物中心,325035 [2]温州医学院药学院分子药理与毒理研究所,325035 [3]温州医学院基础医学院,325035

出　　处：《浙江医学》2011年第3期322-324,327,共4页Zhejiang Medical Journal

基　　金：基金项目：浙江省科技厅实验动物科技计划项目（2009F80004）

摘　　要：目的 检测膳食补充锌改善肝再生是否能通过增加肝细胞核因子-4α （HNF-4α）的表达来实现.方法 选用12周雄性C57BL/6小鼠40只,按随机数字表法分为4组：正常对照组、酒精中毒组、正常补锌组及酒精补锌组,予不同的饮食喂养6个月后通过增殖细胞核抗原（PCNA）阳性标记的肝细胞数目评价肝细胞再生状况,Western blotting法检测HNF-4α蛋白表达,检测超氧化物歧化酶（SOD）及丙二醛（MDA）含量评估肝损伤的氧化应激状态.结果 酒精中毒组小鼠HNF-4α表达减少,与正常对照组小鼠的差异有统计学意义（P＜0.05）,而酒精补锌组小鼠PCNA阳性肝细胞数目增加及HNF-4α蛋白表达水平升高,与酒精中毒组的差异有统计学意义（P＜0.05）.酒精中毒组MDA含量增多,SOD含量下降与正常对照组的差异有统计学意义（P＜0.05）,而酒精补锌组SOD增多,MDA下降,与酒精中毒组的差异有统计学意义（P＜0.05）.结论 长期酒精喂养导致小鼠抗氧化能力下降,而补锌可逆转氧化还原失衡的状态.酒精喂养小鼠补充锌可以增强肝再生,这与HNF-4α的增加有关,膳食补锌可能对酒精性肝病有较好的影响.Objective To examine the effect of dietary zinc supplement on liver regeneration in mice with alcoholic liver disease and its relation to hepatocyte nuclear factor-4 α （HNF-4 α ） expression. Methods Forty adult C57 BL/6 mice were randomly divided into： control, zinc, alcohol and zinc＋alcohol groups. Mice in alcohol and zinc＋alcohol groups were fed with an ethanol-containing liquid diet for 6 months to develop alcoholic liver disease as measured by histopathological changes. Liver regeneration was assessed by immunohistochemical staining of proliferating cell nuclear antigen （PCNA）, and the expression of HNF-4α was determined by Western blotting. Serum malondialdehyde （MDA） and superoxide （SOD） levels were also measured. Results The expression of HNF-4 α in the alcohol group was lower than that in control group （P〈0.05）; while compared with the alcohol group, the PCNA-positive hepatocytes increased significantly, and the expression of HNF-4α also increased in the zinc＋alcohol group. Compared with the control group the serum MDA levels increased significantly in the alcohol group, while the SOD levels declined significantly （P〈0.05）. In the contrast, serum SOD increased and MDA decreased significantly in the zinc＋alcohol group compared with alcohol group （P〈0.05）. Conclusion Long term alcohol exposure can lead to decline antioxidation activity, which can be reversed with the increased HNF-4 α expression by dietary zinc supplement, suggesting that dietary zinc supplementation may be beneficial for alcoholic liver disease.

关 键 词：酒精性肝病 锌 HNF-4Α 

分 类 号：R378.2[医药卫生—病原生物学]