Li Yinbao, Yang Fan, Chen Zuanguang, Shi Lijuan, Zhang Beibei, Pan Jianbin, Li Xinchun, Sun Duanping, Yang Hongzhi
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; School of Pharmaceutical Sciences, Gannan Medical University, Ganzhou, JiangXi, China.
School of Laboratory Medcine, Hubei University of Chinese Medicine, Wuhan, China.
PLoS One. 2014 Apr 14;9(4):e94792. doi: 10.1371/journal.pone.0094792. eCollection 2014.
Pharmaceutical safety testing requires a cheap, fast and highly efficient platform for real-time evaluation of drug toxicity and secondary effects. In this study, we have developed a microfluidic system for phenotype-based evaluation of toxic and teratogenic effects of drugs using zebrafish (Danio rerio) embryos and larvae as the model organism. The microfluidic chip is composed of two independent functional units, enabling the assessment of zebrafish embryos and larvae. Each unit consists of a fluidic concentration gradient generator and a row of seven culture chambers to accommodate zebrafish. To test the accuracy of this new chip platform, we examined the toxicity and teratogenicity of an anti-asthmatic agent-aminophylline (Apl) on 210 embryos and 210 larvae (10 individuals per chamber). The effect of Apl on zebrafish embryonic development was quantitatively assessed by recording a series of physiological indicators such as heart rate, survival rate, body length and hatch rate. Most importantly, a new index called clonic convulsion rate, combined with mortality was used to evaluate the toxicities of Apl on zebrafish larvae. We found that Apl can induce deformity and cardiovascular toxicity in both zebrafish embryos and larvae. This microdevice is a multiplexed testing apparatus that allows for the examination of indexes beyond toxicity and teratogenicity at the sub-organ and cellular levels and provides a potentially cost-effective and rapid pharmaceutical safety assessment tool.
药物安全性测试需要一个廉价、快速且高效的平台，用于实时评估药物毒性和副作用。在本研究中，我们开发了一种微流控系统，以斑马鱼（Danio rerio）胚胎和幼体作为模式生物，基于表型评估药物的毒性和致畸性。该微流控芯片由两个独立的功能单元组成，可对斑马鱼胚胎和幼体进行评估。每个单元都由一个流体浓度梯度发生器和一排七个用于容纳斑马鱼的培养室组成。为了测试这个新芯片平台的准确性，我们检测了一种抗哮喘药物——氨茶碱（Apl）对210个胚胎和210个幼体（每个培养室10个个体）的毒性和致畸性。通过记录一系列生理指标，如心率、存活率、体长和孵化率，定量评估了Apl对斑马鱼胚胎发育的影响。最重要的是，一个名为阵挛惊厥率的新指标，结合死亡率，用于评估Apl对斑马鱼幼体的毒性。我们发现，Apl可在斑马鱼胚胎和幼体中诱导畸形和心血管毒性。这种微型装置是一种多重测试仪器，能够在亚器官和细胞水平检测除毒性和致畸性之外的指标，并提供一种潜在的经济高效且快速的药物安全性评估工具。
