铝负荷致小鼠神经元退行性变与脑内金属离子代谢失衡的关系

Study on the relationship between the metal ion-dyshomeostasis and neurodegeneration caused by the chronic administration of aluminum in mice

目的观察在慢性铝负荷致小鼠神经元退行性变时程中脑内A l3+、Cu2+、Zn2+含量的变化规律,以分析两者的关系。方法采用葡萄糖酸铝溶液(含A l3+400 mg/kg)灌胃给予小鼠,1次/d,5 d/w,连续12 w,建立慢性铝负荷模型。观察小鼠被动回避性学习记忆能力和空间识别能力,脑组织Cu2+、Zn2+、A l3+含量和丙二醛(MDA)水平变化,以及海马神经元的病理形态学改变。结果与相应对照组比,铝负荷第6周后小鼠跳台潜伏期呈时间依赖性进行性缩短而水迷宫寻台时间进行性显著延长,大脑皮层和海马A l3+、Cu2+、Zn2+含量以及MDA水平呈持续升高,海马出现进行性神经元核固缩加重和和神经元丢失。结论脑内金属离子的代谢失衡可能与铝过负荷致神经元退行性变有关。

Objective To explore the relationship between metal ion-dyshomeostasis and the development of neurodegeneration induced by chronically administration of aluminum.Methods Chronic aluminum overload model was established by intragastric administration of aluminum gluconate（equal to Al3＋ 400 mg/kg） to mice once a day,5 times per week for 12 weeks.The learning and memory functions of mice,the contents of Al3＋,Cu2＋,and Zn2＋ as well as malondialdehyde（MDA） levels in brain,and pathologic changes of hippocampus were evaluated by the stepdown test and Morris water maze,inductively coupled plasma-atomic emission spectrometry techniques,and microscopic observation,respectively.Results There existed a shortened step-down latency and the increased seeking platform time, the enhanced the levels of Al3＋,Cu2＋,and Zn2＋ and MDA in both cerebral cortex and hippocampus,and loss and karyopyknosis of neurons in hippocampus in time-dependent manner since the sixth week the aluminum gluconate was consecutively given to mice.Conclusions Chronic aluminum-overloading causes metal ion-dyshomeostasis,which may be responsible for the neuron degeneration of mice.