上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 专题报道（新生儿基础与临床研究） • 上一篇    下一篇

Atp7btx-J小鼠脑组织细胞凋亡及ATP7A表达研究

胡 璟1，焦先婷1，刘晓青2，余晓刚2，何振娟1，张拥军1   

  1. 上海交通大学 医学院附属新华医院 1.新生儿科， 2.上海市儿科医学研究所， 上海 200092
  • 出版日期:2013-07-28 发布日期:2013-08-22
  • 作者简介:胡 璟（1983—），女，硕士生; 电子信箱: happyapplepie@163.com。
  • 基金资助:

    上海市科委基金（06ZR14141）

Cell apoptosis and expression of ATP7A in brain of Atp7btx-J mice

HU Jing1, JIAO Xian-ting1, LIU Xiao-qing2, YU Xiao-gang2, HE Zhen-juan1, ZHANG Yong-jun1   

  1. 1.Department of Neonatology, 2.Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China
  • Online:2013-07-28 Published:2013-08-22
  • Supported by:

    Shanghai Science and Technology Committee Foundation, 06ZR14141

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摘要：

目的 通过对Atp7btx-J小鼠脑组织不同部位细胞凋亡的分析，钙、铜含量的测定，以及铜转运ATP酶ATP7A表达的研究，初步探讨肝豆状核变性致神经系统损伤的作用机制。方法 分离20周龄Atp7btx-J小鼠大脑皮层、小脑、基底神经节及海马区脑组织，Hoechst染色后分析细胞凋亡情况，电感耦合等离子体质谱法测定钙、铜含量，Real-Time PCR检测不同部位ATP7A mRNA的表达量。结果 与野生型小鼠相比，纯合型小鼠小脑及基底神经节区细胞凋亡最为显著（P<0.05），小脑、基底神经节及海马区的铜和钙含量明显升高（P<0.01），脑组织不同部位ATP7A mRNA表达下调，其中基底神经节和小脑部位ATP7A mRNA表达的差异有统计学意义（P<0.05）。结论 肝豆状核变性致神经系统损伤是多因素共同作用的结果，铜在脑内特殊部位的异常蓄积是始动因素，钙介导的细胞凋亡是导致神经系统损伤的重要因素，ATP7A在脑内不能代偿性地协助排出大量蓄积的铜可能加剧了神经系统的损伤。

关键词: 肝豆状核变性, Atp7btx-J小鼠, 脑

Abstract:

Objective To explore the mechanism of nervous system injury in Wilson's disease by analysis of cell apoptosis, determination of concentrations of Ca and Cu and detection of expression of ATP7A in different parts of brain tissues of Atp7btx-J mice. Methods The tissues of cerebral cortex, cerebellum, basal ganglia and hippocampus of Atp7btx-J mice aged 20 weeks were isolated, the cell apoptosis was analyzed after Hoechst staining, the concentrations of Ca and Cu were determined by inductively coupled plasma mass spectrometry, and the expression of ATP7A mRNA in different parts was detected by Real-Time PCR. Results Compared with wild type mice, the cell apoptosis in cerebellum and basal ganglia of homozygous mice was most significant (P<0.05). The concentrations of Ca and Cu in cerebellum, basal ganglia and hippocampus of homozygous mice were significantly higher than those of wild type mice (P<0.01). The expression of ATP7A mRNA in different parts of brains of homozygous mice was lower than that of wild type mice, and there were significant differences between the expression of ATP7A mRNA in basal ganglia and that in cerebellum (P<0.05). Conclusion Many factors contribute to the nervous system damage in Wilson's disease. The abnormal accumulation of Cu in specific parts of the brain is the initiating factor, Ca mediated apoptosis is one of the important factors, and the incompetency of ATP7A in Cu discharge may exacerbate the nervous system damage in Wilson's disease.

Key words: Wilson's disease, Atp7btx-J mouse, brain