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The study on a new therapy of Menkes disease

门克斯病新疗法的研究

基本信息

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

项目摘要

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.

门克斯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多个器官缺铜。相反，铜则积聚在肾脏和肠道中。这些铜分布异常是由铜的膜转运减少引起的。我们研究了皮下注射铜和口服螯合剂（N,N-二乙基氨基甲酸酯）的联合疗法对黄斑小鼠（门克斯病动物模型）铜代谢的影响。【材料与方法】采用4周龄黄斑小鼠和对照小鼠。铜（20μg/次）和氨基甲酸二乙酯（0.05mg/g体重/次）每周两次，持续4周。之后，处死小鼠，获取脑、肝、肾和肠。用原子吸收分光光度计分析这些组织中的铜浓度。还检查了这些组织中细胞色素 C 氧化酶的活性。【结果与讨论】用铜和螯合剂联合治疗的黄斑小鼠的大脑和肝脏中的铜浓度得到改善。接受治疗的黄斑小鼠的肾脏和肠道中的铜浓度没有变化。然而，接受联合治疗的黄斑小鼠的大脑和肾脏中细胞色素C氧化酶的活性降低。这些结果表明，联合疗法改善了铜的分布，但是，该疗法并未改善铜酶活性。