目的 研究两批骨刺片样品对斑马鱼胚胎发育的急性毒性作用。方法 以斑马鱼胚胎为试验对象，观察骨刺片样品A（0.01、0.05、0.10、0.20、0.30、0.50、1.00 mg/mL）、样品B（0.01、0.05、0.10、0.50、1.00、2.00、10.00 mg/mL）对斑马鱼胚胎发育的影响，包括胚胎致畸、致死检测；同时采用超高效液相色谱法-四极杆飞行时间-质谱（UPLC-QTOF-MS）对两批样品所含化学成分进行定性分析。结果 两批样品对斑马鱼胚胎发育的影响相似，主要表现为高浓度下的致死作用，低浓度下主要以发育滞后表型为主；但二者作用浓度存在一定差异，样品A的半数致畸剂量（TD₅₀）为225.4 mg/mL，半数致死剂量（LD₅₀）为292.0 mg/mL；样品B的TD₅₀为60.3 mg/mL，LD₅₀为1.382 mg/mL。UPLC-QTOF-MS分析结果显示，两批样品所含主要化学成分基本一致，但某些成分含量存在一定差异；初步分析显示既是有效成分又是毒性成分的士的宁含量与斑马鱼胚胎试验结果呈正相关。结论 斑马鱼胚胎模型可用于评价骨刺片样品的急性毒性，两批骨刺片样品对斑马鱼胚胎发育影响均表现为高浓度下的致死作用，低浓度下，特别是样品B表现为轻度非正常表型，且均可逆。

Objective To study the acute toxic effect of Guci Tablets on zebrafish embryo development.Methods Zebrafish embryo was used to investigate the development situation under different drug concentrations of two batches of Guci Tablets samples (sample A:0.01, 0.05, 0.10, 0.20, 0.30, 0.50 and 1.00 mg/mL, sample B:0.01, 0.05, 0.10, 0.50, 1.00, 2.00, and 10.00 mg/mL) including embryo teratogenic and lethal tests. Additionally, an UPLC-QTOF-MS was applied to analyze the chemical constituents of both samples.Results The result showed that the effects of both samples on development of zebrafish embryos were similar. The main manifestation was lethal effect under high concentrations and lag phenotypes of development under low concentrations. However, there was a certain difference in the action concentration between both samples, The half of teratogenic dose (TD₅₀) and the half of lethal dose (LD₅₀) of sample A were 0.225 4 mg/mL and 0.292 mg/mL, respectively; the TD₅₀ and the LD₅₀ of sample B were 0.060 3 mg/mL and 1.382 mg/mL, respectively. According to the results of UPLC-QTOF-MS, the main chemical constituents contained in both samples were basically in agreement. But there were some differences in the content of some constituents. And the preliminary analysis showed there was a positive correlation between the content of strychnine and the toxicity evaluation result by zebrafish embryo experiment. Conclusion The result indicated that the zebrafish embryo model was suitable for the toxicity evaluation of Guci Tablets. The effects of two batches of Guci Tablets on zebrafish embryonic development were lethal at high concentrations, and slightly abnormal phenotypes at low concentrations, especially sample B, all of which were reversible.

国家十二五“重大新药创制”专项课题（2014ZX09304307-002）