药物性肝损伤（druginducedliverinjury，DILI）可分为固有型与特异质两类，是导致新药撤市、急性肝衰竭的主要诱因。布洛芬作为常用非甾体抗炎药，常规治疗剂量肝毒性较低，大剂量或长期暴露可诱发肝损伤，属于固有型DILI模型。酒精共暴露可显著放大其肝毒性，以氧化应激为核心机制，伴随活性氧蓄积、抗氧化系统失衡、凋亡与炎症激活。动物实验存在明显性别差异，雄性动物肝损伤表型更显著，该模型可用于非甾体抗炎药肝毒性及保肝药物评价。^[1-2]

图1. 布洛芬处理后雌雄小鼠肝脏中糖酵解与脂肪酸通路相关酶的水平及表达变化^[1]

布洛芬诱导动物肝损伤模型参考：^[2-5]

造模成功关键指标：血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）水平显著升高。

参考文献：

[1] Tiwari, Shuchita, et al. Gender0Specific Changes in Energy Metabolism and Protein Degradation as Major Pathways Affected in Livers of Mice Treated with Ibuprofen. Scientific Reports, vol. 10, no. 1, 2020, p. 3386.

[2] AlKandari, Fajer M., et al. Protective Effects of Propolis and Chitosan Nanoparticles against Ibuprofen0Induced Hepatotoxicity in Albino Rats. Diseases, vol. 12, no. 3, 2024, p. 49.

[3] Ilic, Spomenko, et al. Ibuprofen Hepatic Encephalopathy, Hepatomegaly, Gastric Lesion and Gastric Pentadecapeptide BPC 157 in Rats. European Journal of Pharmacology, vol. 667, 2011, pp. 3220329.

[4] Wen, Congcong, et al. Metabolism of Liver CYP450 and Ultrastructural Changes after Long0Term Administration of Aspirin and Ibuprofen. Biomedicine & Pharmacotherapy, vol. 108, 2018, pp. 2080215.

[5] Wen, Congcong, et al. Metabolism of Liver CYP450 and Ultrastructural Changes after Long0Term Administration of Aspirin and Ibuprofen. Biomedicine & Pharmacotherapy, vol. 108, 2018, pp. 2080215.