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目的:探索不同类型药物性肝损伤的发病机制及保肝解毒颗粒的干预机理。方法:160只小鼠随机分为雷公藤多苷、异烟肼及四环素组各50只,空白对照组10只。各实验组再分为单纯模型组,保肝解毒颗粒大、中、小剂量组和甘利欣对照组,每组10只。分别以相应剂量药物灌胃5天,然后以雷公藤多苷、异烟肼及四环素灌胃1次造模。检测小鼠血清白介素-18(IL-18)水平及肝细胞凋亡情况。结果:雷公藤多苷和四环素模型组小鼠血清IL-18水平分别为均高于空白对照组,差异有显著性意义(P<0.05);肝细胞凋亡程度严重,与空白组比较,差异有显著性意义(P<0.05)。保肝解毒颗粒中、小剂量可使雷公藤多苷模型小鼠IL-18水平明显降低,大、中剂量可使其肝细胞凋亡显著减轻;保肝解毒颗粒各剂量均可使四环素性模型小鼠IL-18水平明显降低,小剂量可使其肝细胞凋亡程度明显减轻。异烟肼模型组及各观察组小鼠血清IL-18水平均无明显变化,肝细胞凋亡程度较轻,与空白组比较,差异均无显著性意义(P>0.05)。结论:不同类型药物性肝损伤的发生机理有所不同;雷公藤多苷和四环素所致的急性肝损伤与IL-18和肝细胞凋亡密切相关;保肝解毒颗粒可通过降低血清IL-18水平、抑制肝细胞凋亡等起到防治肝脏损害的作用。
Objective: To explore the pathogenesis of different types of drug-induced liver injury and the intervention mechanism of Baogan Jiedu Granules. METHODS: A total of 160 mice were randomly divided into triptolide, isoniazid and tetracycline groups, 50 in each group and 10 in the blank control group. Each experimental group was further divided into a simple model group, Baogan Jiedu Granule large, medium, and small dose groups and Ganlixin control group, 10 in each group. The rats were given intragastric administration of the corresponding dose of the drug for 5 days, and then the rats were intragastrically administered once with triptolide, isoniazid, and tetracycline. The levels of serum interleukin-18 (IL-18) and hepatocyte apoptosis were detected in mice. RESULTS: Serum levels of IL-18 were higher in tripterygium glycosides and tetracycline models than in the blank control group, with significant differences (P<0.05). The degree of hepatocyte apoptosis was severe and compared with the blank group. There was significant significance (P<0.05). Low and medium doses of Baogan Jiedu Granules can significantly reduce the levels of IL-18 in the model mice of Tripterygium wilfordii, and the large and medium doses can significantly reduce the apoptosis of hepatocytes; Baogan Jiedu Granules can make tetracycline model at different doses. The level of IL-18 in mice was significantly reduced, and a small dose could significantly reduce the degree of hepatocyte apoptosis. There was no significant change in serum IL-18 levels in the isoniazid model group and each observation group, and the degree of hepatocyte apoptosis was mild. Compared with the blank group, there was no significant difference (P>0.05). Conclusion: The mechanism of different types of drug-induced liver injury is different. The acute liver injury caused by tripterygium glycosides and tetracycline is closely related to IL-18 and apoptosis of hepatocytes; Baogan Jiedu Granules can reduce serum IL-18 levels. Levels, inhibition of hepatocyte apoptosis, etc. play a role in the prevention and treatment of liver damage.