Evaluation of the protective effect of Rhei Radix et Rhizoma against α-naphthylisothiocyanate induced liver injury based on metabolic profile of bile acids.
Evaluation of the protective effect of Rhei Radix et Rhizoma against α-naphthylisothiocyanate induced liver injury based on metabolic profile of bile acids.
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DOI：
10.1016/j.jep.2012.09.049
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发表时间：
2012-12-18
影响因子：
5.4
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Yang F;Xu Y;Xiong A;He Y;Yang L;Wan YJ;Wang Z
目的：通过胆汁酸(BAS)代谢谱、生化指标和组织学改变，评价大黄(Rhei Radix Et Rhizoma)对异硫氰酸异硫氰酸酯(α-naphthylisthiinedate，ANIT)所致肝损伤的保护作用。采用超高效液相色谱-四极杆质谱联用技术(UPLC-MS)测定BAs的浓度，然后进行主成分分析(PCA)和偏最小二乘判别分析(PLS-DA)的多元统计分析。根据主成分分析结果，可明确区分为载药组、ANIT组和Rho+ANIT组。牛磺胆酸(TCA)、牛磺酸-猪去氧胆酸(THDCA)、甘胆酸(GCA)和甘鹅脱氧胆酸(GCDCA)是大黄抗肝损伤和保护作用的最重要的标志物，这一点在偏最小二乘法中得到了进一步的证实。上述指标与血清天冬氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)呈正相关，提示TCA、THDAC、GCA、GCDCA可作为敏感的生物标志物。BAS含量的变化可用来评价ANIT所致的肝毒性及大黄的保护作用。为进一步研究大黄的胆汁淤积机制及治疗作用奠定了基础。
To evaluate the hepatoprotective effect of the root and rhizome of Rhubarb (Rhei Radix et Rhizoma) against α-naphthylisothiocyanate (ANIT)-induced liver injury using metabolic profile of bile acids (BAs) along with biochemical parameters and histological alterations. Ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS) was applied to determinate the concentration of BAs, which was followed by multivariate statistical analysis of Principal Component Analysis (PCA) and Partial Least Squares Discriminate Analysis (PLS-DA). Based on PCA results, three groups (Vehicle group, ANIT group and RhO + ANIT group) were clearly distinguished. Tauro-cholic acid (TCA), tauro-hyodesoxycholic acid (THDCA), glyco-cholic acid (GCA), and glyco-chenodeoxycholic acid (GCDCA) were proved to be the most important markers corresponding to ANIT-induced liver injury and protection provided by Rhubarb, which is further confirmed by PLS-DA. A correlation was found between the foregoing BAs and biochemical parameters including serum aspartate aminotransferase (ALT) and aspartate aminotransferase (AST), which confirmed that TCA, THDAC, GCA, and GCDCA could be considered as sensitive biomarkers. The variance of the BAs contents can be used to evaluate ANIT-induced hepatotoxicity caused by ANIT and protective effects of Rhubarb. It also lays the foundation for the further research on the mechanisms of cholestasis as well as the therapeutic effect of Rhubarb.
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