目的 研究對乙酰氨基酚（APAP）對斑馬魚幼魚的肝臟毒性，并驗證斑馬魚模型用于藥物肝毒性快速評價的實用性。方法 以發(fā)育72 hpf的肝臟熒光轉基因斑馬魚幼魚（L-FABP：EGFP）為實驗對象，不同濃度的APAP分別處理斑馬魚幼魚，于處理后24、48、72 h，體視顯微鏡下觀察幼魚的死亡率、肝臟形態(tài)學變化和卵黃囊吸收情況，熒光顯微鏡下觀察APAP對幼魚肝臟熒光的影響。結果 APAP對斑馬魚幼魚存活率的影響呈劑量和時間相關性。APAP處理后的幼魚肝臟形態(tài)出現(xiàn)異常、肝臟顏色變暗，卵黃囊腫。與空白對照組相比，APAP處理后的幼魚肝組織L-FABP熒光表達明顯下降，肝臟明顯萎縮退化。結論 APAP對斑馬魚幼魚具有肝臟毒性。肝臟熒光轉基因斑馬魚模型快速評價藥物的肝臟毒性具有較好的應用前景。

Objective To determine the hepatotoxicity of acetaminophen (APAP) in larval zebrafish and to validate the practicability of zebrafish model for rapid assessment of drug hepatotoxicity. Methods 72 hpf liver fluorescence transgenic zebrafish larvae (L-FABP: EGFP) were administered with APAP at four dosage series for 24, 48, and 72 h, respectively. Larval zebrafish mortality, liver morphology, yolk sac retention, and changes in liver fluorescence were evaluated to study the hepatotoxic effects of APAP. Results The effect of APAP on mortality of larval zebrafish was dose- and time-dependent. Larval zebrafish treated with APAP exhibited liver malformation, discoloration, hepatatrophia, and vitelline cyst. Compared with the control group, the liver fluorescence intensity significantly decreased in the larval zebrafish treated with APAP. Conclusion APAP could induce the liver damage in larval zebrafish. And using zebrafish as a reliable mammal model for screening hepatotoxic agents has good application prospects.

國家自然科學基金（81202584），山東省科學院青年科學基金項目（魯科院字2012第100號）資助