五酯片不同给药间隔抵抗扑热息痛所致肝损伤的作用及机制研究  

Wuzhi Tablet protects against APAP-induced liver injury at different pretreated intervals in mice

作　　者：徐乐千 周艳莹 姜伊鸣 邢云惠 黄民 毕惠嫦 XU Le-qian;ZHOU Yan-ying;JIANG Yi-ming;XING Yun-hui;HUANG Min;BI Hui-chang(Lab of Drug Metabolism and Pharmacokinetics,School of Pharmaceutical Sciences,Sun Yat-sen University,Guangzhou 510006,China)

机构地区：[1]中山大学药学院,药物代谢与药动学实验室,广东广州510006

出　　处：《药学学报》2021年第4期1147-1154,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81973392,82025034)。

摘　　要：扑热息痛(paracetamol)又称对乙酰氨基酚(acetaminophen,APAP),其导致的药源性肝损伤在世界范围内普遍存在。五酯片(南五味子醇浸膏,Wuzhi Tablet,WZ)是临床上常用的护肝药。作者前期研究表明,WZ预处理三天后与APAP同时给药可抵抗APAP所致肝损伤,但单次给予WZ与APAP不同给药间隔对肝损伤的作用及机制尚不清楚。本文研究了单次给予WZ与APAP不同间隔给药后的肝损伤指标变化、APAP代谢物生成情况和细胞色素P450(cytochrome P450,CYP450)代谢酶活性,考察了WZ单次不同给药间隔抵抗APAP所致肝损伤的作用及机制。动物实验经中山大学动物伦理委员会审核通过。结果表明,单次给予WZ 0、0.5及2 h后再给予APAP,均可显著减轻APAP所致肝损伤,其机制为抑制CYP450酶介导的APAP代谢激活,减少APAP毒性代谢物的生成。本研究进一步确证了WZ与APAP间隔0、0.5及2 h给药具有显著抵抗APAP所致肝损伤的作用,WZ通过抑制APAP代谢激活相关的CYP450酶活性,从而抵抗APAP所致肝损伤,为五酯片防治APAP所致肝损伤提供新数据。Acetaminophen(APAP,also known as paracetamol)-induced liver injury is the leading cause of drug-induced liver injury in the world.Wuzhi Tablet(WZ,an ethanol extract of Schisandra sphenanthera)is widely used in clinical practice to protect liver function.Our previous studies have shown that pretreatment with WZ for 3 days can significantly protect against APAP-induced liver injury;however,the effect of different intervals between APAP and WZ treatment on APAP-induced liver injury remains unclear.In this study,the change in liver injury indexes,APAP metabolites,and the activity of cytochrome P450(CYP450)enzymes after treatment with WZ and APAP at different intervals were determined.The animal experiment was reviewed and approved by the Animal Ethics Committee of Sun Yat-sen University.The results show that 0 h,0.5 h,and 2 h pretreatment with WZ significantly protected against APAP-induced liver injury in mice,as evidenced by a significant decrease in biochemical parameters such as alanine aminotransferase(ALT),aspartate aminotransferase(AST),and malonaldehyde(MDA).WZ inhibited the metabolic activation of APAP mediated by CYP450 enzymes and reduced the formation of APAP metabolites.This study further demonstrates that pretreatment with WZ at different intervals(0 h,0.5 h,and 2 h before APAP dosing)exerts a significant hepatoprotective effect against APAP-induced liver injury,and a single-dose of WZ inhibits the activity of CYP450 enzymes related to APAP metabolic activation,thereby protecting against APAP-induced hepatotoxicity.

关 键 词：五酯片 对乙酰氨基酚 药源性肝损伤 给药间隔 CYP450代谢酶 

分 类 号：R917[医药卫生—药物分析学]