黄药子诱导肝损伤大鼠血清脂肪酸的代谢轮廓  

The metabolic profile of serum fatty acids in rats with Rhizoma Dioscoreae Bulbiferae-induced liver injury

作　　者：熊印华[1] 徐英[2] 杨莉[2] 王峥涛[2] 

机构地区：[1]江西科技师范大学药学院,江西南昌330013 [2]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上海市复方中药重点实验室,上海201203

出　　处：《药学学报》2017年第5期753-759,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81660692);江西省教育厅青年科学基金项目(GJJ14598)

摘　　要：中药黄药子具有肝毒性,黄药子诱导的肝损伤大鼠的血清脂肪酸代谢轮廓尚不清楚。本文采用气相-质谱联用技术定量分析空白组、黄药子醇提物(ethanol extraction,ET)组和黄独素B(diosbulbin B,DB)组大鼠血清中16种游离脂肪酸(non-esterified fatty acids,NEFA)和酯化脂肪酸(esterified fatty acids,EFA),借助化学计量学方法分析大鼠灌胃黄药子或黄独素B后血清中脂肪酸代谢轮廓的变化。NEFA含量测定结果显示,DB组棕榈酸、硬脂酸、棕榈油酸、油酸、异油酸、亚油酸、亚麻酸、二十碳三烯酸、花生四烯酸和二十二碳六烯酸含量显著降低;ET组亚油酸和二十碳三烯酸含量显著升高,花生四烯酸、二十二碳六烯酸含量显著降低。EFA含量测定结果显示,ET组和DB组棕榈酸、硬脂酸、花生四烯酸、二十碳五烯酸和二十二碳六烯酸含量显著降低。主成分分析表明,ET组和DB组的大鼠血清脂肪酸代谢轮廓明显偏离正常水平,且ET组偏离程度大于DB组。偏最小二乘法-判别分析表明,花生四烯酸和二十二碳六烯酸对ET和DB的肝毒性具有重要贡献,且与谷丙转氨酶、谷草转氨酶和总胆红素具有良好的相关性,被鉴定为黄药子肝毒性的潜在生物标识物。本研究为深入研究黄药子的肝毒性的分子作用机制奠定基础。Rhizoma Dioscoreae Bulbiferae is a traditional Chinese medicine with hepatotoxicity, but the metabolic profile of fatty acids has not been identified in the rats with liver injury. In this project, a gas chromatography-mass spectrometry method was applied to simultaneous quantification of 16 non-esterified fatty acids （NEFA） and esterified fatty acids （EFA） in the serum of control, ethanol extraction of Rhizoma Dioscoreae Bulbiferae （ethanol extraction, ET） and diosbulbin B （DB）-treated rats. Meanwhile, the change of fatty acid metabolic profile of liver injured rats was analyzed by principal component analysis （PCA） and partial least squares-discriminant analysis （PLS-DA）. The results of NEFA concentration indicated that the serum concen- trations of palmitic acid （C16 ： 0）, stearic acid （C18 ： 0）, palmitoleic acid （C16 ： ln7）, oleic acid （C18 ： ln9）,vaccenic acid （C18 ： ln7）, linoleic acid （C18 ： 2n6）, linolenic acid （C18 ： 3n3）, eicosatrienoic acid （C20 ： 3n6）, arachidonic acid （C20 ： 4n6） and docosahexaenoic acid （C22 ： 6n3） in DB-treated rats decreased significantly, while that of C18 ： 2n6 and C20 ： 3n6 obviously increased and that of C20 ： 4n6 and C22 ： 6n3 noticeably dropped in ET-treated rats when compared with control. Furthermore, the results of EFA concentration illus- trated that the serum concentrations of C16 ： 0, C18 ： 0, C20 ： 4n6, C22 ： 6n3 and eicosapentaenoic acid （C20 ： 5n3） in two toxic groups were remarkably decreased when compared with control. The fatty acid meta- bolic profiles of the two toxic groups exhibited significant difference from the normal levels, and the degree of deviation of ET group was higher than that of DB group. More importantly, the results of PLS-DA showed that C20 ： 4n6 and C22 ： 6n3 were important indicators of the hepatotoxicity induced by ET and DB, and the serum concentrations of the two fatty acids had good correlation with the levels of alanine aminotra

关 键 词：脂肪酸 黄药子 黄独素B 肝毒性 

分 类 号：R969[医药卫生—药理学]