论文部分内容阅读
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 establish a high-throughput screening method for neurotoxic substances based on primary hippocampal neuron models and evaluate the method. Methods High-content screening was used to quantitatively determine the effects of 11 drugs on the cell number, mitochondrial mass, Mn SOD level, γH2AX level and neurite outgrowth in primary hippocampal neurons. Results Simvastatin, doxepin, diazepam, chlorpheniramine, and clozapine caused mitochondrial changes in cell viability, Mn SOD level and γH2AX level increased, and cell processes became shorter. Estazolam Mitochondria decreased, inhibited the growth of cell protrusions; phenobarbital promote cell neurite growth; aspirin caused mitochondrial quality decline; ephedrine caused γH2AX levels. Conclusion Compared with the existing data in the literature, neurotoxicity detection accuracy is high, which can provide reference for further neurotoxicity evaluation and neural mechanism research.