【作者】 邱红梅； 何百成； 周歧新； 杨俊卿；

【Author】 QIU Hongmei, et al (Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016 China)

【机构】 重庆市生物化学与分子药理学重点实验室重庆医科大学；

【摘要】 目的:采用经胃肠道给药的慢性铝中毒模型,观察铝过负荷致神经元退行性变与脑内铁、锰离子水平的关系,探讨慢性铝中毒致神经元退行性变的可能机制。方法:给予小鼠氯化铝溶液(相当于400 mg·kg-1 Al3+)灌胃,每天1次,1周6天,共3个月,建立铝过负荷所致的小鼠神经元退行性变模型。观测其被动回避性学习记忆能力和空间识别能力的改变; 大脑皮层和海马金属铁、锰离子含量变化以及海马病理学的改变。结果:铝过负荷可致小鼠学习记忆功能出现明显障碍(明暗刺激试验结果显示铝负荷组潜伏期明显缩短;水迷宫结果显示铝负荷组寻台时间明显延长)。金属离子检测中,铝过负荷组脑组织皮层与海马的铁、锰含量较对照组明显升高,且呈现一定的时效关系;多元逐步回归分析发现:铁、锰离子对小鼠学习记忆能力有显著的损伤作用。病理切片显示:铝过负荷可导致小鼠海马神经元的明显丢失和核固缩。结论:慢性铝过负荷可导致小鼠神经元出现明显退行性变,且学习记忆能力下降。其机制可能与铝过负荷引起脑内铁、锰等金属离子代谢紊乱有关。更多还原

【Abstract】 Obejective: To observe the relationship between Mn, Fe ions levels and neurodegeneration induced by chronic administration of aluminum in mice and its mechanism. Methods: The neurodegenerative model of mice was established via intragastric administration of AlCl3 solution (element aluminum 400 mg/kg) once a day, with 6 d a week for 3 months. The light-dark test and morris-water-maze were used to evaluate the learning and memory functions. Inductively coupled plasma atomic emission spectrometry were used to determine the levels of metal ions. Pathomorphological changes of hippocampi were observed. Results: Aluminum overload significantly decreased capacity of passive avoidance learning and memory and spatial recognition, caused the pyknosis and neuron loss of hippocampi, and parallelly increased the contents of Mn and Fe ions in both of cortices and hippocampi increased in time-dependent manner in aluminum overloading mice, compared with corresponding control. Positive relativities were observed among the learning and memory dysfunction and the levels of Mn and Fe ions from chronic aluminum overload in mice. Conclusion: Aluminum overload markedly causes neurodegeneration and damages learning and memory function in mice, its mechanism may be related to the increasing levels of iron and manganes in brain induced by aluminum overload.更多还原