基于原代海马神经元的神经毒性物质高内涵筛选方法的研究  

Application of high content screening in studying drug induced neurotoxicity based on primary hippocampal neurons

作　　者：于红燕[1] 祁妍敏[1] 李学会[2] 董莉莎[2] 姚碧云[2] 

机构地区：[1]中国民用航空局民用航空医学中心/民航总医院/民航医学研究所,北京100123 [2]北京大学公共卫生学院毒理学系

出　　处：《毒理学杂志》2016年第5期363-369,共7页Journal of Toxicology

基　　金：民航科技项目(MHRD201042)

摘　　要：目的建立基于原代海马神经元模型的神经毒性物质高通量筛选方法,并对该方法进行评价。方法应用高内涵筛选技术定量检测11种药物对原代海马神经元的细胞数量、线粒体质量、Mn SOD水平、γH2AX水平和神经突起生长等参数的影响。结果安眠酮、多虑平、地西泮、氯苯那敏和氯氮平等在抑制细胞存活的同时,引起线粒体质量改变,Mn SOD水平、γH2AX水平升高,细胞突起变短;艾司唑仑使线粒体质量下降,抑制细胞突起生长;苯巴比妥促进细胞神经突起生长;阿司匹林引起线粒体质量下降;麻黄碱引起γH2AX水平升高。结论与文献已有数据进行比较,神经毒性检测正确率高,可为进一步的神经毒性评价及神经机制研究提供参考。Objective To estalish high-througth put screening based on neurotoxic substances primary hippocampal neurons model method,and the method was evaluted. Methods High content screening was applied to detect the effects of 11 drugs on cell count,mitochondria mass,Mn SOD,γH2AX and neurite outgrowth. Results Methaqualone,doxepin,diazepam,chlorpheniramine and clozapine inhibited cell survival,while causing mitochondrial mass change,increased levels of Mn SOD and γH2AX,and neurite shorten. Estazolam induced mitochondria degradation and neurite outgrowth inhibition. Phenobarbital promoted neurite outgrowth. Aspirin caused mitochondrial mass decline. Ephedrine elevated levels of γH2AX. Conclusion Compared with existing literature and data,the accuracy of neurotoxicity detection is high. The method can provide a reference for further evaluation and study of the neural mechanisms of neurotoxicity.

关 键 词：高内涵 原代海马神经元 神经毒性 

分 类 号：R730.21[医药卫生—肿瘤] R329.2[医药卫生—临床医学]