The study on a new therapy of Menkes disease

门克斯病新疗法的研究

• 批准号: 10670759
• 负责人: KODAMA Hiroko
• 金额: $ 1.98万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670759/
• 关键词: Menkes disease; copper; chelating agent; threatment; macular mouse; macular マウス; 銅輸送ATPase; 銅投与; シチオカーボ; Menkes disease; copper; chelating agent; threatment; macular mouse; macular マウス; 銅輸送ATPase; 銅投与; シチオカーボ

Menkes disease is a neurodegenerative disorder characterized by a copper deficiency in various organs including the brain and liver. On the contrary, copper accumulated in the kidney and intestine. These abnormalities of copper distribution are caused by a reduced membrane-transport of copper. We examined effects of a combination therapy of a subcutaneous copper administration and an oral administration of a chelating agent (N,N-diethyl carbamirate) on copper metabolism in the macular mouse, an animal model of Menkes disease. 【Materials and Methods】 Four weeks old macular mice and control mice were used. Copper (20μg/time) and diethyl carbamirate (0.05 mg/g body weight/time) were given twice a week for 4 weeks. After that, the mice were sacrificed, and the brain, liver, kidney and intestine were obtained. Copper concentrations in those tissues were analyzed with an atomic absorption spectrophotometer. The activity of cytochrome C oxidase in those tissues was also examined. 【Results and Discussion】 The copper concentration were improved in the brain and liver of macular mice that were treated with a combination of copper and a chelating agent. The copper concentrations were not changed in the kidney and intestine of the treated macular mice. However, the activities of cytochrome C oxidase were decreased in the brain and kidney of macular mice that were treated with the combination therapy. These results suggest that copper distribution was improved with the combination therapy, however, the copper enzyme activities were not improved by the therapy.

Menkes病是一种神经退行性疾病，其特征是包括大脑和肝脏在内的各种器官中的铜缺乏症。相反，铜积聚在肾脏和肠内。这些铜分布的异常是由铜的膜转移降低引起的。我们检查了皮下铜给药的组合疗法和螯合剂的口服给药（N，N，N-二乙基氨基甲酸酯）对Masular Mouse（Menkes疾病动物模型）中铜代谢的影响。 [材料和方法]使用了四周大的黄斑小鼠和对照小鼠。每周两次给出两次铜（20μg/time）和甲基氨基甲酸酯（0.05 mg/g体重/时间）4周。之后，处死小鼠，并获得大脑，肝脏，肾脏和肠。用原子吸收分光光度计分析这些组织中的铜浓度。还检查了这些尖端中细胞色素C氧化酶的活性。 [结果和讨论]在黄斑小鼠的大脑和肝脏中，铜浓度得到了改善，这些小鼠用铜和螯合剂的组合进行了处理。在处理过的黄斑小鼠的肾脏和肠中，铜浓度没有改变。然而，在用联合疗法治疗的黄斑小鼠的大脑和肾脏中，细胞色素C氧化酶的活性得到了改善。这些结果表明，通过联合疗法改善了铜分布，但是，铜酶活性并未通过治疗改善。