为什么吃药会伤肝呢？科学家对小鼠做了什么？！

背景介绍药物性肝损伤druginducedliverinjuryDILI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]动物信息给药方式给药方案C57BL/6J小鼠饮水100mg/kg/天连续7天8-10周龄雄性Wistar大鼠灌胃400mg/kg/天连续5天8-10周龄雄性Wistar大鼠灌胃400mg/kg/天连续4周200-250g雄性Wistar大鼠灌胃15mg/kg/天连续4周200g雄性Wistar大鼠腹腔注射400mg/kg/天连续4周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。药物性肝损伤模型2相关产品推荐分类货号英文名称机制造模药SJ-MX2156Ibuprofen抑制线粒体β‑氧化与辅酶A形成硫酯产生大量活性氧SJ-MX2156AIbuprofen L-lysineSJ-MX2156BIbuprofen sodium治疗药SJ-BP0342BPC 157逆转布洛芬所致肝肿大显著降低血清AST、ALT水平SJ-MN3993Silymarin抗氧化、抗凋亡、抗炎参考文献[1]Tiwari, Shuchita, et al. Gender-Specific 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 Ibuprofen-Induced 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 BPC157 in Rats.European Journal of Pharmacology, vol.667, 2011, pp.322-329.[4]Wen, Congcong, et al. Metabolism of Liver CYP450 and Ultrastructural Changes after Long-erm Administration of Aspirin and Ibuprofen.Biomedicine Pharmacotherapy, vol.108, 2018, pp.208-215.[5]Wen, Congcong, et al. Metabolism of Liver CYP450 and Ultrastructural Changes after Long-Term Administration of Aspirin and Ibuprofen.Biomedicine Pharmacotherapy, vol.108, 2018, pp.208-215.来自于公开发表的文献仅供参考所有产品仅用于工业应用或者科学研究等非医疗目的不可用于人类 或动物的临床诊断或治疗非药用非食用