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目的探讨基于随机双盲交叉试验的心理认知测试和基于细胞模型的高内涵筛选方法在药物航空安全性评价中的应用。方法随机双盲交叉试验后测试艾司唑仑对志愿者心理认知的影响,应用高内涵筛选技术定量检测艾司唑仑对PC12和大鼠海马神经元细胞多参数的影响。结果飞行心理品质5个项目和基本认知能力1个项目的得分,安慰剂组显著优于艾司唑仑组。艾司唑仑在300~1000μmol/L使PC12细胞的数量、面积以及宽度均减少,使海马神经元的线粒体质量减少;在1000μmol/L时,使PC12细胞的圆度和γH2AX荧光强度增加、线粒体质量减小。结论基于随机双盲交叉试验的心理认知测试灵敏准确,可作为药物评价的确认方法;而基于细胞的高内涵神经毒性筛选低成本、无损伤、高通量,具有成为药物初筛方法的潜力。
Objective To investigate the application of psychological cognitive test based on randomized double-blind crossover test and high content screening method based on cell model in the evaluation of aviation safety of drugs. Methods A randomized double-blind crossover test was conducted to evaluate the effect of estazolam on the psychological perception of volunteers. The high-content screening technique was used to quantitatively test the influence of estazolam on the multi-parameters of hippocampal neurons in PC12 and rats. RESULTS: Five items of flight quality and one item of basic cognitive ability were significantly better in the placebo group than in the eszoconn group. Estazolam reduced the number, area and width of PC12 cells in 300 ~ 1000μmol / L, and decreased the mitochondrial mass of hippocampal neurons. At 1000μmol / L, the roundness and γH2AX fluorescence intensity of PC12 cells increased, and mitochondria Reduced quality. Conclusions Psychological cognitive tests based on randomized double-blind crossover test are sensitive and accurate and can be used as confirmation methods for drug evaluation. However, the screening of low-cost, non-invasive and high-throughput cell-based high-content neurotoxicity has the potential of becoming a drug screening method .