基于二相代谢酶考察何首乌中主要单体肝毒性  

Study on the hepatotoxicity of monomers in Polygoni Multiflori Radix on the basis of the inhibition of two-phase metabolic enzymes

作　　者：汪祺[1] 张玉杰[2] 戴忠[1] 马双成[1] WANG Qi ZHANG Yu-jie DAI Zhong MA Shuang-cheng(National Institutes for Food and Drug Control, Beijing 100050, China Beijing University of Chinese Medicine, Beijing 100102, China)

机构地区：[1]中国食品药品检定研究院,北京100050 [2]北京中医药大学,北京100102

出　　处：《药物分析杂志》2016年第12期2120-2124,共5页Chinese Journal of Pharmaceutical Analysis

基　　金：国家自然科学基金(81503347)

摘　　要：目的:以胆红素代谢过程中UDP-葡萄糖醛酸转移酶1A1(UGT1A1酶)介导的胆红素葡萄糖醛酸结合环节为切入点,考察何首乌中主要单体成分肝毒性。方法:以胆红素为UGT1A1酶底物,以表观抑制常数Ki为评价指标,采用体外肝微粒体孵育法测定待测单体成分肝毒性有无及大小。结果:大黄素对于UGT1A1酶有强抑制作用Ki=(5.400±0.956)μmol·L^(-1)(*P<0.05);二苯乙烯苷对于UGT1A1酶抑制作用较弱,Ki=(48.054±1.568)μmol·L^(-1)(*P<0.05),抑制类型均为竞争型抑制,而大黄酸几乎没有抑制作用。结论:本实验所建立的体外研究方法稳定可行,提示大黄素为何首乌中潜在致肝毒性成分。Objective： To investigate the hepatotoxicity of monomers in Polygoni Multiflori Radix based on the bilirubin metabolism mediated by glucuronidation of UDP-glucuronosyltransferases 1A1 （UGT1A1 enzyme）.Methods： The monomers were added into the human liver microsomes to test the hepatotoxicity using the bilirubin as UGT1A1 enzyme substrate, and the inhibition of the UGT1A1 enzyme was investigated.In the microsomes incubation systems, the apparent inhibition constant Ki was adopted to evaluate the hepatotoxicity.Results： Emodin showed a strong inhibition effect on the UGT1A1 enzyme and Ki= （5.400±0.956） μmol·L-1 （＊P〈0.05）.THSG has a weak inhibition effect on the UGT1A1 enzyme and Ki= （48.054±1.568） μmol·L-1 （＊P〈0.05）.Both of the above inhibition types was the competitive inhibition, while Rhein almost has no inhibition effect on the UGT1A1 enzyme.Conclusion： The method established in our study is stable and feasible.All the results point out that the emodin is a potentially toxic component.

关 键 词：何首乌 大黄酸 大黄素 胆红素葡萄糖醛酸结合物 肝毒性 UDP-葡萄糖醛酸转移酶1A1 代谢酶 人肝微粒体 表观抑制常数 中药安全性 

分 类 号：R917[医药卫生—药物分析学]