目的 研究兩批骨刺片樣品對斑馬魚胚胎發(fā)育的急性毒性作用。方法 以斑馬魚胚胎為試驗對象，觀察骨刺片樣品A（0.01、0.05、0.10、0.20、0.30、0.50、1.00 mg/mL）、樣品B（0.01、0.05、0.10、0.50、1.00、2.00、10.00 mg/mL）對斑馬魚胚胎發(fā)育的影響，包括胚胎致畸、致死檢測；同時采用超高效液相色譜法-四極桿飛行時間-質(zhì)譜（UPLC-QTOF-MS）對兩批樣品所含化學成分進行定性分析。結(jié)果 兩批樣品對斑馬魚胚胎發(fā)育的影響相似，主要表現(xiàn)為高濃度下的致死作用，低濃度下主要以發(fā)育滯后表型為主；但二者作用濃度存在一定差異，樣品A的半數(shù)致畸劑量（TD₅₀）為225.4 mg/mL，半數(shù)致死劑量（LD₅₀）為292.0 mg/mL；樣品B的TD₅₀為60.3 mg/mL，LD₅₀為1.382 mg/mL。UPLC-QTOF-MS分析結(jié)果顯示，兩批樣品所含主要化學成分基本一致，但某些成分含量存在一定差異；初步分析顯示既是有效成分又是毒性成分的士的寧含量與斑馬魚胚胎試驗結(jié)果呈正相關。結(jié)論 斑馬魚胚胎模型可用于評價骨刺片樣品的急性毒性，兩批骨刺片樣品對斑馬魚胚胎發(fā)育影響均表現(xiàn)為高濃度下的致死作用，低濃度下，特別是樣品B表現(xiàn)為輕度非正常表型，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.

國家十二五“重大新藥創(chuàng)制”專項課題（2014ZX09304307-002）