Wilson病模型TX小鼠Cu^(2+)代谢相关转运因子的观察  

Observation of copper ion metabolism related transfer factor in Wilson’s disease model toxic milk mice

作　　者：唐彬[1] 张薇[1] 付新录[1] 赵勇[1] 黎福荣[1] TANG Bin;ZHANG Wei;FU Xin-lu;ZHAO Yong;LI Fu-rong(Laboratory Animal Center of Sun Yat-sen University,Guangzhou,Guangdong 510006,China)

机构地区：[1]中山大学实验动物中心,广东广州510006

出　　处：《热带医学杂志》2021年第10期1265-1270,共6页Journal of Tropical Medicine

基　　金：广东省科技基础条件建设项目(2013B060300010)。

摘　　要：目的研究TX小鼠ATP7B变异诱导的铜异常代谢与CTR1、ATP7A及ATP7B蛋白的关系。方法运用RT-PCR技术对1~12月龄TX小鼠肝脏、肾脏、脑组织中CTR1 mRNA、ATP7A mRNA、ATP7B m RNA的含量进行定量检测,同时运用Western bolt技术对其相应的CTR1、ATP7A及ATP7B蛋白进行定量检测,最后运用原子吸收分光光度法定量测定各脏器组织中铜离子含量。结果肝ATP7A mRNA、ATP7B mRNA,肾脏CTR1 mRNA、ATP7A m RNA、ATP7B m RNA的含量逐月减少,除肝脏CTR1 mRNA外其余每月mRNA的含量与翻译成的蛋白含量成相同的趋势;肝肾脑中铜离子含量最高峰分别达到937、544、252 mg/kg,仅肝脏铜离子与其CTR1 mRNA呈对应负相关性谷峰状波动。结论当脏器铜离子含量蓄积高达到900 mg/kg上下时,机体启动负反馈调节,显著降低CTR1 mRNA含量进行控铜。TX小鼠作为模型应用不受月龄限制,但Wilson病早期干预治疗以拮抗铜转运蛋白失代偿对减轻肝细胞的损害,外源性间接或直接助力Cu^(2+)转运因子的协调作用是重要的。Objective To investigatethe relationship between the expression of protein CTR1,ATP7 A and ATP7 B and the abnormal metabolism of copper ion in TX mouse induced by ATP7 B mutation. Methods RT-PCR and Western Bolt technique were used to quantitative the amount of CTR1 mRNA,ATP7 A mRNA,ATP7 B mRNA and the protein CTR1,ATP7 A and ATP7 B in 1-12 months SPF TX mouse’s liver,kidney and brain. Atomic spectrophotometer technique was used to test copper ion accumulation. Results The content of liver ATP7 A mRNA,ATP7 B mRNA,kidney CTR1 mRNA,ATP7 A mRNA,and ATP7 B mRNA decreased month by month,except for liver CTR1 mRNA. The monthly mRNA content was in the same trend as the translated protein content. The highest peaks of copper ion content in the liver,kidney and brain reached 937,544,and 252 mg/kg,respectively. Only the liver copper ion and its CTR1 mRNA showed a corresponding negatively correlated fluctuation. Conclusions When the copper ion content of the organs accumulated up to 900 mg/kg,the body initiated negative feedback regulation,which significantly reduced the CTR1 mRNA content to control copper ion. TX mice were not limited by the age as a model. Early intervention and treatment of Wilson disease to decompensate of copper transporters could reduce the damage of hepatocytes,and it should be important for exogenous indirect or direct assistance to coordinate the role of Cu^(2+) transporters.

关 键 词：TX小鼠 铜离子 CTR1 ATP7A ATP7B 

分 类 号：R742.4[医药卫生—神经病学与精神病学]