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- 4α (HNF- 4α ) 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- 4α 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- 4α expression by dietary zinc supplement, suggesting that dietary zinc supplementation may be beneficial for alcoholic liver disease.
展开▼
