药学学报, 2011, 46(1): 39-44
引用本文:
徐 英 陈崇崇 杨 莉 王君明 季莉莉 王峥涛 胡之璧. 基于胆汁酸代谢网络分析中药黄药子的肝毒性[J]. 药学学报, 2011, 46(1): 39-44.
XU Yang, Chen-Chong-Chong, Yang- Chi, Wang-Jun-Meng, Ji-Chi-Chi, Wang-Zheng-Chao, Hu-Zhi-Bi. Evaluation on hepatotoxicity caused by Dioscorea bulbifera based on analysis of bile acids[J]. Acta Pharmaceutica Sinica, 2011, 46(1): 39-44.

基于胆汁酸代谢网络分析中药黄药子的肝毒性
徐 英1, 陈崇崇1, 杨 莉1, 2*, 王君明1, 季莉莉1, 2, 王峥涛1, 2*, 胡之璧1
(1. 上海中医药大学中药研究所 中药标准化教育部重点实验室暨中药新资源与品质评价国家中医药管理局重点研究室, 上海 201210; 2. 上海中药标准化研究中心, 上海 201210)
摘要:

 本文采用超高效液相色谱质谱联用 (UPLC-MS) 胆汁酸代谢网络分析方法评价黄药子乙醇提取物 (ethanol extraction, ET) 和单体化合物黄独素B (diosbulbin B, DB) 致小鼠的肝毒性。通过小鼠毒性实验, ETDB给药组小鼠都可见明显的肝脏毒性。血清胆汁酸含量测定结果经主成分分析后, 空白组和给药组区分明显, ETDB给药组矢量方向一致, 但两者之间也有一定距离, 提示DB是黄药子致肝毒性的主要毒性成分之一。经偏最小二乘法-判别分析后, 结果表明牛磺酸结合型胆汁酸对表征ETDB致小鼠肝毒性具有重要的贡献, 且以牛磺酸结合型为主的胆汁酸与ALTAST具有很好的相关性, 因此以牛磺酸结合型为主的胆汁酸可作为评价黄药子致小鼠肝毒性的生物标识物。本研究为进一步深入评价黄药子致肝毒性及致毒机制研究奠定了基础。

关键词:   
Evaluation on hepatotoxicity caused by Dioscorea bulbifera based on analysis of bile acids
Abstract:

Metabolic profile of bile acids was used to evaluate hepatotoxicity of mice caused by ethanol extraction of Dioscorea bulbifera L. (ethanol extraction, ET) and diosbulbin B (DB), separately.  Ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS) was applied to determine the contents of all kinds of endogenous bile acids including free bile acids, taurine conjugates and  glycine conjugates.  Obvious liver injuries could be observed in mice after administrated with ET and DB.  Based on the analysis using principle components analysis (PCA), toxic groups could be distinguished from their control groups, which suggested that the variance of the contents of bile acids could evaluate hepatotoxicity caused by ET and DB.  Meanwhile, ET and DB toxic groups were classified in the same trends comparing to control groups in the loading plot, and difference between the two toxic groups could also be observed.  DB proved to be one of the toxic components in Dioscorea bulbifera L.  Bile acids of tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), taurodeoxycholic acid (TDCA), cholic acid (CA) and others proved to be important corresponds to ET and DB induced liver injury according to analysis of partial least square-discriminant analysis (PLS-DA) and the statistical analysis showed that there were significant differences between the control groups and toxic groups (P < 0.01).  Furthermore, good correlation could be revealed between the foregoing bile acids and ALT, AST.  It indicated that taurine conjugated bile acids as TUDCA, TCDCA, TCA and TDCA along with CA could be considered as sensitive biomarkers of ET and DB induced liver injury.  This work can provide the base for the further research on the evaluation and mechanism of hepatotoxicity caused by Dioscorea bulbifera L.

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