中药与临床2026，Vol.17Issue(2)：20-28,44,10.
十八味牛黄清肝丸防治对乙酰氨基酚致小鼠急性肝损伤的量效关系及调控Keap1-Nrf2通路抗氧化应激的作用机制
The dose-effect relationship of Shibawei Niuhuang Qinggan Pills in the treatment of acute liver injury induced by acet-aminophen in mice and the mechanism of regulating Keap1-Nrf2 pathway against oxidative stress
王中元 1李一叶 1李然 2张霆 1王张 2王芳洁 1黄艳 1扎西革白 2付嘉庆 1宋贵丽 1白白 2韩梦恬 1张敬文2
作者信息
- 1. 成都中医药大学药学院,四川成都 611137
- 2. 成都中医药大学民族医药学院,四川成都 611137
- 折叠
摘要
Abstract
Objective:To explore the optimal clinical dosage of Shibawei Niuhuang Qinggan Pills and its mechanism of action in the treatment of acute liver injury induced by acetaminophen(APAP).Methods:The 2.5 times clinical dose(83.33 mg·kg-1·d-1),5 times clinical dose(166.66 mg·kg-1·d-1),10 times clinical dose(333.33 mg·kg-1·d-1),20 times clinical dose(666.66 mg·kg-1·d-1)and 40 times clinical dose(1 333.32 mg·kg-1·d-1)of Shibawei Niuhuang Qinggan Pills were used for preventive administration,once a day for 7 days.The APAP acute liver injury model was replicated 12 h after the last administration,and the animals were sacrificed after 12 h.The appearance and histopathological changes of the liver were observed,and the Suzuki pathological score was per-formed.The levels of liver function in serum and oxidative stress indexes in liver tissue were tested.The expression levels of Keap1,Nrf2,HO-1,NQO1,GCLC and GCLM genes and proteins were tested by PCR and WB.Results:Shibawei Niuhuang Qinggan Pills can improve APAP-induced acute liver injury in mice,and 10 times clinical dose group has the best effect.It can improve the appear-ance of the liver and the pathological changes of liver tissue,reduce the levels of liver function indexes such as ALT,AST,TBIL and DBIL in serum,increase the levels of antioxidant indexes such as SOD and GSH in liver,and reduce the levels of MDA and GSSG in liver tissue.It can also reduce the gene and protein expression levels of Keap1 and GCLM in liver tissue,and increase the gene and protein expression levels of Nrf2,HO-1,NQO1 and GCLC oxidative stress indicators.Conclusion:Shibawei Niuhuang Qing-gan Pills can improve APAP-induced acute liver injury,and the clinical dosage(2.00 g·60 kg-1·d-1)is reasonable.Its mechanism may be related to the regulation of Keap1-Nrf2 pathway anti-oxidative stress.关键词
十八味牛黄清肝丸/对乙酰氨基酚/急性肝损伤/量效关系/Keap1-Nrf2通路/氧化应激Key words
Shibawei Niuhuang Qinggan Pills/acet-aminophen/acute drug-induced liver injury/dose-effect rela-tionship/keap1-Nrf2 pathway/oxidative stress分类
医药卫生引用本文复制引用
王中元,李一叶,李然,张霆,王张,王芳洁,黄艳,扎西革白,付嘉庆,宋贵丽,白白,韩梦恬,张敬文..十八味牛黄清肝丸防治对乙酰氨基酚致小鼠急性肝损伤的量效关系及调控Keap1-Nrf2通路抗氧化应激的作用机制[J].中药与临床,2026,17(2):20-28,44,10.
