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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 major monomer constituents in Polygonum multiflorum Thunb., A bilirubin glucuronide-binding pathway mediated by UDP-glucuronosyltransferase 1A1 (UGT1A1 enzyme) during bilirubin metabolism. Methods: With bilirubin as the UGT1A1 enzyme substrate and apparent inhibition constant Ki as the evaluation index, the presence and size of hepatotoxicity of the monomer components to be tested were determined by in vitro liver microsomal incubation. RESULTS: Emodin had a strong inhibitory effect on UGT1A1 (Ki = 5.400 ± 0.956 μmol·L -1) (* P <0.05). Stilbene inhibited the UGT1A1 enzyme activity significantly (Ki = 48.054 ± 1.568) μmol·L -1 (* P <0.05). The inhibitory types were all competitive inhibition, while rhein had almost no inhibitory effect. Conclusion: The in vitro research method established in this study is stable and feasible, suggesting that emodin is the potential cause of hepatotoxicity.