基于高分化PC12细胞的神经毒性物质高内涵筛选方法的研究  

Study of high content screening in drug induced neurotoxicity based on high differentiated PC12 cells

作　　者：祁妍敏[1] 李学会[2] 董莉莎[2] 高雅[2] 刘文丽[2] 赵鹏[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,北京100025 [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3期173-178,共6页Journal of Toxicology

基　　金：民航科技项目(MHRD201042)

摘　　要：目的建立基于高分化PC12细胞模型的神经毒性物质高内涵筛选方法,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种药物对高分化PC12细胞的细胞数量、线粒体质量、细胞核面积、细胞膜通透性、Mn SOD水平、γH2A.X水平、细胞面积、细胞圆度、细胞宽度、细胞长度和细胞宽长比等参数的影响。结果安眠酮、多虑平和地西泮等在抑制细胞存活的同时,引起线粒体质量改变,膜通透性增大,Mn SOD水平、γH2A.X水平升高,细胞长度减小、圆度增大、面积减小等;苯巴比妥、异戊巴比妥能够促进细胞存活或促进细胞神经突起生长。结论与文献已有数据进行比较,神经毒性检测正确率高,多参数表征的一般毒性较单一参数表征的一般毒性检测正确率要高。可使用高分化PC12细胞作为高内涵筛选的神经毒性评价模型,以细胞数量、线粒体质量、Mn SOD水平和γH2A.X水平作为细胞毒性指标,以细胞宽长比作为神经毒性指标,对神经毒性物质进行有效筛选。Objective To study drug induced neurotoxicity based on high differentiated PC12 cells by high content screening.Methods High content screening was applied to detect cell count,mitochondria mass,nucleus area,membrane permeability,Mn SOD,γH2A. X,cell area,cell roundness,cell width,cell length and cell width to length. Results Methaqualone,Doxepin,diazepam,chlorpheniramine maleate and clozapine induced cell loss, mitochondria mass changed, membrane permeability increasing, Mn SOD,γH2A. X levels rising,cell shorten and round; Phenobarbitaland amobarbital increased cell number or cell length. Conclusion Compared with literature data,the detection accuracy of neurotoxicity is high. And the detection accuracy of general toxicity with single-parameter is lower than with multi-parameter. High differentiated PC12 cells can be used to detect drug induced neurotoxicity combined with high content screening.

关 键 词：高内涵 高分化PC12细胞 神经毒性 

分 类 号：R994[医药卫生—毒理学]