斑马鱼中高通量毒性测试方法研究进展和应用现状

Research Progress and Application of Middle/High-throughput Toxicity Testing Methods Using Zebrafish

基于哺乳动物的传统毒性测试方法存在周期长、成本高、通量低、有动物伦理限制等诸多问题。斑马鱼因为个体小、发育快、易于饲养等特点,适用于构建基于多孔板的中高通量毒性测试方法。本文对基于多孔板的斑马鱼急性毒性、发育毒性、行为和微行为分析等几个中高通量测试方法进行了综述,分析了各自的优缺点及应用现状。另外介绍了高通量测试在自动化操作方面的最近进展。最后分析了斑马鱼中高通量毒性测试方法未来的发展趋势和应用前景,提出应着重开展对现有方法的验证和优化工作,减少对人工的依赖,实现自动化操作和标准化分析,同时开发可更敏感检出发育毒性的分子或者信号通路的测试指标。随着斑马鱼高通量毒性测试方法不断的发展和优化,其在化学物质毒性筛查和风险评估中将发挥越来越重要的作用。

Traditional mammalian-based toxicity testing methods have many drawbacks such as long test duration,high cost,low throughput and animal ethical restrictions.Zebrafish is suitable for the construction of high-throughput toxicity testing methods due to its outstanding features,such as being smaller in size,rapid growth and easy to feed.In this paper,existing middle and high throughput testing methods for analyzing the acute toxicity,development toxicity and behaviors of zebrafish based on porous plates were reviewed,and their advantages,disadvantages and application status were analyzed.Recent research progress on automatic operations for high-throughput testing was also introduced.The development trend and application prospects of middle/high-throughput toxicity testing methods using zebrafish were discussed as well.It is believed that the validation and refinement of existing m ethods should be emphasized to improve automation and standardization,Meanwhile,more refined molecular or signaling pathway endpoints for sensitive detection of developmental toxicity should be developed.It is foreseeable that zebrafish-based middle/high-throughput testing methods will play significant roles in toxicity screening and risk assessment of chemicals.