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

Metabonomic study of intervene effect of Xiaoyao Powder on rats with hepatic fibrosis

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 Xi- aoyao Powder liquid through intragastric administration to intervene and hepatic tissues were used for histopathologi- cal 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 trTptophan were sig- nificantly 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.