铜过量小鼠肝损伤模型的建立及各项指标的观察研究

目的探讨昆明小鼠在不同剂量的铜负荷时所引起的肝脏抗氧化水平和相关病理的改变。方法32只昆明小鼠平均分为4组,第1组为对照组,每天灌胃生理盐水2次,第2、3、4组作为实验组,分别用不同浓度(12.8、25.6和38.4mg/mL)的硫酸铜每日灌胃2次,16周后,观察肝组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)以及谷胱甘肽过氧化物酶(GSH-Px)的活性,测定血清谷丙转氨酶(ALT)和谷草转氨酶(AST)以及血清和肝组织中铜含量,并做肝脏病理以及电镜检查。结果与正常对照组相比,实验组肝组织中MDA含量明显升高(P<0.05),而SOD和GSH-Px活性明显下降(P<0.05);血清ALT、AST活性以及血清、肝脏铜含量明显升高(P<0.05);病理组织学检查可见高剂量铜灌胃组小鼠肝细胞变性坏死以及少量铜颗粒沉积;电镜提示肝细胞核、线粒体等细胞器异常,并可见铜颗粒。结论过量的铜可对肝脏造成损害,其机制可能与释放出的铜离子介导脂质过氧化而造成肝脏损害有关。其病变过程与Wilson's病相似,可为进一步研究铜代谢异常等疾病提供动物模型。

Establishment of Mouse Model of Liver Damage Induced by Excessive Copper

Objective To investigate the changes of antioxidant level and pathology in liver damage induced by different doses of CuSO4 in Kunming mice. Method Thirty two mice were equally divided into 4 groups. Mice in the first group were intragastrically administrated with physiological saline twice each day as control. Mice in the second,third and fourth group were respectively intragastrically administrated with 12.8,25.6 and 38.4 mg/mL of CuSO4 twice each day for 16 weeks. The levels of malondialdehyde (MDA),superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the liver,concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the sera and copper levels in the liver and sera were measured. Pathohistological analysis of the liver was also performed. Result Comparing with the control group,levels of MDA in liver,concentrations of ALT and AST in sera,and copper levels in liver and sera of mice administrated with Cu were dramatically increased (P <0.05),and the activities of SOD and GSH-Px in liver were significantly decreased (P <0.05). The pathohistological examination. Results showed that mice in the experimental group had necrosis of hepatic cells and Cu scatter in liver. Under electron microscope,the mitochondria were swelled and nuclear showed abnormality. Conclusion Excessive copper can cause severe damage of the liver by causing lipid peroxidation. The pathological changes in mice liver by excessive Cu are similar with Wilson's disease which provides a model for research on metabolic abnormality of copper.