对乙酰氨基酚诱导的小鼠药物性肝损伤的模型研究

The Model of Acute Liver Injury Induced by Acetaminophen in Mice

改良对乙酰氨基酚(acetaminophen,APAP)单独诱导小鼠急性肝损伤的模型和致死模型。随机将小鼠分为4组:空白对照组、APAP 3 h组、APAP 6 h组和APAP 12 h组,每组5只。饥饿15 h后用对乙酰氨基酚诱发小鼠肝损伤。测定各组血清ALT、AST及胆红素含量,HE染色观察各组肝组织损伤情况。观察生存率时,小鼠随机分为对照组、禁食+APAP(500 mg/kg)组、禁食+APAP(300 mg/kg)组和不禁食+APAP(500 mg/kg)组,四组同时给药,然后记录各组小鼠的生存情况,绘制四组小鼠的生存曲线。小鼠注射APAP后,随时间的延长,ALT、AST水平逐渐升高,均明显高于空白对照组(P<0.05)。小鼠肝脏HE染色可见,APAP中毒组小鼠肝细胞坏死及炎性细胞浸润。禁食+APAP(500 mg/kg)组小鼠自16 h开始出现死亡,72 h时全部死亡,死亡率明显高于不禁食组和禁食+APAP(300 mg/kg)组小鼠。该研究对APAP引起的C57/BL6小鼠药物性肝损伤模型进行改良,使其更加稳定和便于研究,为进一步探究APAP诱导肝毒性的机制及防治措施奠定了基础。

The aim of the study was to improve the acute liver injury model and lethal model of mice induced by acetaminophen （APAP） injection. 20 mice were divided into 4 groups randomly： normal control, APAP 3 h group, APAP 6 h group, and APAP 12 h group. Mice were fasted for 15 hours before APAP injection to induce liver injury. We assayed serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and examined liver pathologic changes after APAP injection by HE staining. 20 mice were divided into four groups： control group, fast＋APAP （500 mg/kg） group, fast＋APAP （300 mg/kg） group and non-fast＋APAP （500 mg/kg） group. The four groups were administrated at the same time. We observed the survival status of mice before and after APAP administration and made survival curve. Serum ALT and AST levels increased by time after APAP administration and were significantly higher than that in control group （P〈0.05）. Liver specimens of APAP mice displayed characteristic centrilobular necrosis and inflammatory infiltration. All mice of fast＋APAP （500 mg/kg） group died within 16 to 72 hours, and the mortality was significantly higher than those of the other 3 groups. Our study suecessfully improved acute liver injury model and lethal model of C57/BL6 mice induced by APAP, which laid the foundation for further exploration of mechanism and control measures ofAPAP-induced hepatotoxicity.