锌对海马神经元毒性作用的机制研究  

Mechanism of zinc neurotoxicity to hippocampal neurons in vitro

作　　者：朱林[1,2] 纪详军[1,2] 潘灏[1,2] 王汉东 杭春华[1,2] 成惠林[1,2] 孙康健[1,2] 樊友武[1,2] 史继新[1,2] 

机构地区：[1]南京军区南京总医院中国人民解放军全军神经外科研究所 [2]南京大学医学院,江苏南京210002

出　　处：《中华神经外科疾病研究杂志》2014年第2期137-141,共5页Chinese Journal of Neurosurgical Disease Research

基　　金：国家自然科学基金资助项目(81070974);中国博士后基金资助项目(201150M1572)

摘　　要：目的大量文献报道,锌在诸多神经系统疾病所致的神经元死亡过程中发挥了重要作用,但具体机制不清。本实验拟对锌的神经元毒性机制进行体外实验研究。方法在体外培养的海马神经元中加入锌(或)锌阻断剂,利用相差显微镜从形态学观察神经元损伤;Western blot法检测p38、泛素化蛋白的表达;用MTT(methyl thiazolyl tetrazolium)比色法定量分析神经元的损伤;再加入锌和(或)p38抑制剂,观察泛素化蛋白表达的变化。结果锌对体外培养的海马神经元有明显的毒性作用;锌以明显的浓度依赖和时间依赖的方式诱导海马神经元中泛素化蛋白、p38的升高;抑制p38可减少锌诱导的泛素化蛋白的表达。结论高浓度的锌对神经元有毒性作用,它可能激活p38信号通路影响蛋白降解并最终导致神经元损伤。Objective Increasing amount of evidence has shown that excessive zinc release plays a key role in inducing neuronal death during central nervous system disease,but the underlying mechanisms are poorly understood.Here the mechanism of zinc neurotoxicity to hippocampal neurons in vitro hippocampus was studied.Methods Zinc and/or specific block agent were applied on cultured hippocampal neurons.The neural damage was morphological assessed by phase contrast microscope.The p38 and ubiquitination were detected by Western blot.The neural damage was quantitatively analyzed by methyl thiazolyl tetrazolium （MTT）.Then zinc and/or SB239063 （block agent of p38） was applied and the ubiquitination was detected.Results Cultured hippocampal neurons were vulnerable to increased extracelhlar zinc levels.Zinc induced ubiquitination and p38 in cultured neurons in a concentration-and time-dependent manner.SB239063 could reduce the zinc-induced ubiquitination.Conclusion All these findings indicate the neurotoxicity of high concentration of zinc to neurons,which may be associated with the activation of p38 leading to the protein degradation.

关 键 词：神经元 泛素 锌 

分 类 号：R741.02[医药卫生—神经病学与精神病学]