艾司唑仑对中枢神经系统影响的评价方法研究

Study on Two Evaluation Methods of Estazolam Effects on Central Nervous System

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 study the psychological cognitive test based on randomized double-blind crossover trial and high content screening method based on cell models in medicine aviation safety evaluation. Methods After randomized double-blind crossover trial,the effects of estazolam on cognitive psychology of volunteers were tested,and high content screening method was applied to measure the effects of estazolam on multiple parameters of PC12 cells and hippocampal neurons. Results The scores of five parameters from flight psychological quality test and one parameter from basic cognitive test were significantly superior in estazolam group than in placebo group. 300 -1000 μmol / L estazolam reduced the number,area and width of PC12 cells and the mitochondrial mass of hippocampal neurons; 1000 μmol / L estazolam increased the roundness and γH2AX fluorescence intensity and reduced the mitochondrial mass of PC12 cells. Conclusion The psychological cognitive test based on randomized double-blind crossover trial is sensitive and accurate,so it may be used as confirmation method of medicine evaluation; the high content screening method based on cell models is low-cost,noninvasive and high throughput,so it may be used as a method of medicine screening.