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    玄参总苷成分分析及其干预大鼠甲亢阴虚火旺证模型的血清代谢组学研究

    Analysis of Total Glycosides in Scrophulariae Radix and Intervention of Serum Metabolomics in Hyperactivity of Fire Due to Yin Deficiency of Rat Model

      摘要
    • 摘要:
      目的 探讨玄参总苷的主要化学成分及其干预大鼠甲亢阴虚火旺证模型的作用机制。
      方法 将SD大鼠随机分为对照组、模型组、玄参总苷给药组。腹腔注射3′,5-三碘代-L-甲状腺原氨酸(3,5,3'-triiodothyronine，T3)溶液100 μg·(100 g)−1建立阴虚火旺模型，进行环磷酸腺苷(cyclic adenosine monophosphate，cAMP)、环磷酸鸟苷(cyclic guanosine monophosphate，cGMP)水平等相关指标的检测，采用超高效液相色谱-四极杆-飞行时间串联质谱技术(ultra high performance liquid chromatography-quadrupole-time of flight mass spectrometry，UHPLC-Q-TOF-MS)对玄参总苷的化学成分和不同组别大鼠的血清内源性代谢物进行分析，并结合主成分分析(principal component analysis，PCA)和正交偏最小二乘判别分析(orthogonal partial least squares -discriminant analysis，OPLS-DA)，筛选差异性代谢物并构建其代谢通路。
      结果 从玄参总苷中共鉴定了31个化学成分，玄参总苷能显著降低阴虚大鼠cAMP、cAMP/cGMP水平，阴虚火旺模型大鼠血清中25个内源性代谢物发生显著变化，其中鞘脂、类固醇、脂质、亚油酸、花生四烯酸呈上升趋势，通路分析表明玄参总苷可能通过调节鞘脂类、甘油磷脂、花生四烯酸等代谢途径改善阴虚火旺证候。
      结论 本研究运用血清代谢组学方法揭示了玄参总苷干预甲亢阴虚火旺证的作用机制，为玄参“滋阴降火”功效的物质基础和临床应用提供了理论依据。

       

      Abstract:
      OBJECTIVE  To explore the main chemical components of total glycosides in Scrophulariae Radix and the mechanism of their intervention in the model of syndrome of hyperactivity of fire due to Yin deficiency in rats.
      METHODS SD rats were randomly divided into control group, model group, and total glycosides of Scrophulariae Radix group. 3,5,3'-Triiodothyronine(T3) solution was injected intraperitoneally100 μg·(100 g)−1 to establish hyperactivity of fire due to Yin deficiency model, and cyclic adenosine monophosphate(cAMP) and cyclic guanosine monophosphate(cGMP) levels were detected. Ultra high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) technology was used to analyze the chemical components of total glycosides of Scrophulariae Radix and endogenous serum metabolites from different groups. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) multivariate statistical analysis were applied to screen differential metabolites and construct its metabolic pathway.
      RESULTS A total of 31 chemical constituents were identified from the total glycosides of Scrophulariae Radix, which significantly reduced the levels of cAMP and cAMP/cGMP in rats with Yin deficiency. Additionally, in the Yin deficiency-induced fire hyperactivity model, 25 endogenous metabolites showed significantly changes, including increased levels of sphingolipids, steroids, lipids, linoleic acid, and arachidonic acid. Pathway analysis indicated that total glycosides of Scrophulariae Radix might improve hyperactivity of fire due to Yin deficiency disease by regulating metabolic pathways such as sphingolipids, glycerophospholipids, and arachidonic acid.
      CONCLUSION In this study, serum metabolomics method is used to reveal the mechanism of total glycosides of Scrophulariae Radix in the intervention of syndrome of hyperactivity of fire due to Yin deficiency, which provide a theoretical basis for the material basis and clinical application of Scrophulariae Radix’s nourishing yin for lowering fire effect.

       

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