逍遥散对实验性肝纤维化大鼠模型干预作用的代谢组学研究

目的： 运用代谢组学方法探讨逍遥散对大鼠肝纤维化保护作用的机理。 方法： 雄性Wistar大鼠连续9周皮下注射40% CCl₄橄榄油溶液制备肝纤维化模型，灌胃给予逍遥散水煎液进行干预，取肝组织进行病理学检查，以柱前衍生-气质联用技术检测大鼠血清代谢产物变化，运用偏最小二乘判别分析法（PLS-DA）、正交偏最小二乘判别法（OPLS-DA）等多元技术分析差异代谢产物，根据网络数据库，解析相应内源性代谢物的变化机理。 结果： 与空白组比较，模型组大鼠肝组织明显破坏，胶原纤维增加。血清中乳酸、磷脂、丝氨酸、苏氨酸、葡萄糖、酪氨酸、亚油酸、色氨酸等浓度均显著升高，给予逍遥散后各项指标均明显回调。 结论： 逍遥散对于肝纤维化具有较好的治疗作用，改善肝功能、调节脂肪酸代谢、促进氨基酸生成等多方面作用可能是其治疗肝纤维化的作用机理。

Objective: To conduct a metabonomic study in rats with hepatic fibrosis and the hepato-intervene effect of Xiaoyao Powder in rats. Methods: Male Wistar rats were injected subcutaneously with 40% CCl₄ olive oil solution for 9 weeks to prepare the hepatic fibrosis model.After the model was established,the rats were given Xiaoyao Powder liquid through intragastric administration to intervene and hepatic tissues were used for histopathological examination.Pre-column derivatization-GC-MS was used to detect changes in rat serum metabolites.PLS-DA,OPLS-DA and other diversified techniques were used to analyze different metabolites.The change mechanism of endogenous metabolite was explored based on the network database. Results: Compared with blank group,in model group rat hepatic tissues were significantly destroyed,and the collagenous fiber was remarkably increased.Concentrations of lactic acid,phospholipid,serine,threonine,glucose,tyrosine,linoleic acid and tryptophan were significantly increased in serum.All the indicators were significantly recovered after receiving Xiaoyao Powder. Conclusion: Xiaoyao Powder has better effect on hepatic fibrosis,improving hepatic function,adjusting aliphatic acid metabolism,and promoting amino acid generation may be its mechanism of treatment of hepatic fibrosis.