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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。
Chinese medicine Xanthium has hepatotoxicity, the yellow fatty acid-induced liver injury in rats serum fatty acid profile is not clear. Gas chromatography-mass spectrometry (GC-MS) was used to quantitatively analyze 16 kinds of free fatty acids (NEFA) in the serum of rats in blank group, ethanol extraction (ET) group and diosbulbin B ) And esterified fatty acids (EFA). The stoichiometrical changes of fatty acid profiles in the serum of rats fed with Radix Astragali or Radix B were analyzed by stoichiometry. The results of NEFA assay showed that DB group palmitic acid, stearic acid, palmitoleic acid, oleic acid, isoleic acid, linoleic acid, linolenic acid, eicosatrienoic acid, arachidonic acid and docosahexa The content of linoleic acid and eicosatrienoic acid in ET group increased significantly, while the content of arachidonic acid and docosahexaenoic acid in ET group decreased significantly. The content of palmitic acid, stearic acid, arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid in ET group and DB group were significantly decreased by EFA assay. Principal component analysis showed that the profiles of serum fatty acid metabolism in ET and DB groups were significantly deviated from the normal level, and the deviation of ET group was greater than DB group. Partial Least Squares - Discriminant analysis showed that arachidonic acid and docosahexaenoic acid have an important contribution to the hepatotoxicity of ET and DB, and have a good correlation with alanine aminotransferase, aspartate aminotransferase and total bilirubin , Has been identified as potential biomarkers of xanthoxamine hepatotoxicity. This study lays the foundation for the further study on the molecular mechanism of action of xanthium-induced hepatotoxicity.