基于GC-MS代谢组学的牛黄解毒片配伍减毒机制研究

Study on the Detoxification Mechanism of Niuhuang Jiedu Tablets Based on GC-MS Metabolomics

    摘要
  • 摘要:
    目的 采用气相色谱-质谱联用(GC-MS)的代谢组学技术探讨牛黄解毒片复方配伍的减毒作用及机制。
    方法 将24只小鼠随机分为空白组、雄黄组(1.0 g·kg-1)和牛黄解毒片组(7.8 g·kg-1)，每组8只，连续口服给药14 d，采集各组小鼠的肝脏和肾脏，观察病理形态学变化；测定肝脏中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和肾脏中肌酐(Cr)、尿酸(UA)的含量；GC-MS代谢组学分析肝脏和肾脏中内源性代谢物的差异。
    结果 与雄黄组比较，牛黄解毒片组小鼠肝脏中ALT、AST和肾脏中Cr、UA含量发生显著变化(P＜0.05)，肝脏和肾脏病理损伤减轻；筛选出柠檬酸、抗坏血酸、天冬酰胺、左旋多巴、苯丙氨酸等17种与减毒相关的生物标志物，涉及谷氨酰胺和谷氨酸代谢、精氨酸的生物合成、色氨酸代谢、酪氨酸和色氨酸的生物合成、苯丙氨酸代谢等通路。
    结论 牛黄解毒片复方配伍降低了雄黄的肝肾毒性，减毒作用可能与回调氨基酸代谢有关。

     

    Abstract:
    OBJECTIVE To study the toxicity-reducing effects and mechanisms of Niuhuang Jiedu Tablets (NHJDT) by gas chromatography-mass spectrometry (GC-MS) metabolomics.
    METHODS 24 mice were randomly divided into control, realgar (1.0 g·kg-1) and NHDJT (1.0 g·kg-1) groups with 8 mice in each group. The liver and kidney of mice were collected for pathologic examination after 14 d oral administration to mice. The content of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in liver and creatinine (Cr) and uric acid (UA) in kidney was also determined. The differences of endogenous metabolites in liver and kidney were further analyzed by GC-MS metabolomics.
    RESULTS The contents of ALT and AST in the liver as well as the Cr and UA in kidney of mice were significantly changed after NHJDT intervention (P < 0.05). NHJDT alleviated the pathological damage of liver and kidney in mice. A total of 17 biomarkers related to detoxification were screened, including citric acid, ascorbic acid, asparagine, levodopa and phenylalanine. The changes of metabolites mainly involved in glutamine and glutamate metabolism, arginine biosynthesis, tryptophan metabolism, tyrosine and tryptophan biosynthesis, and phenylalanine metabolism.
    CONCLUSION NHJDT with compound compatibility could reduce the hepatorenal toxicity of realgar. The detoxification mechanism may be related to the regulation of amino acid metabolism.

     

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