高国瑗 郑希元 彭渊 陶艳艳 刘平 杨涛 刘成海

[摘要]探讨扶正化瘀胶囊（Fuzheng Huayu capsules，FHC）对二甲基亚硝胺（dimethylnitrosamine，DMN）诱导的肝纤维化模型大鼠血清代谢组学的影响。应用液质联用技术分别建立对照组、模型组和FHC组的大鼠血清代谢图谱，并定量分析各组内源性代谢物——氨基酸和胆汁酸水平。实验结果表明，FHC组大鼠的血清代谢指纹谱与模型组存在显著差异，采用主成分分析（PCA）和偏最小二乘法（PLSDA）初步鉴定了潜在5种溶血磷脂胆碱类生物标记物。再通过定量分析各组大鼠血清氨基酸和胆汁酸的水平，发现FHC治疗4周后血清中失调的14种氨基酸和5种胆汁酸水平明显有回归正常水平的趋势。由此可见，FHC抗肝纤维化作用机制可能涉及到溶血磷脂胆碱类、氨基酸和胆汁酸的代谢过程。

[关键词]扶正化瘀；肝纤维化；代谢组学；液质联用；生物标记物

[Abstract]To investigate the effect of Fuzheng Huayu capsule（FHC） on serum metabolomics in rats with liver fibrosis induced by dimethylnitrosamine（DMN） The metabolic profiles of rat serum of normal group， model group， and FHC group were established by liquid chromatographymass spectrometry technology Furthermore， the levels of endogenous metabolites such as amino acids and bile acids were measured in each group The results showed that there were significant differences in the serum metabolic fingerprints between the FHC group and the model group Moreover， 5 potential lysophosphatidylcholines biomarkers were identified by using principal component analysis（PCA） and partial least squares discriminant analysis （PLSDA） Quantitative analysis of amino acids and bile acids in serum of rats showed that 14 kinds of amino acids and 5 kinds of bile acids returned to normal levels after four weeks of FHC treatment In conclusion， the antihepatic fibrosis mechanisms of FHC may be related to the metabolic process of lysophosphatidylcholines， amino acids and bile acids

[Key words]Fuzheng Huayu capsules； liver fibrosis； metabolomics； UPLCMS/MS； biomarker

doi：10.4268/cjcmm20160925

扶正化瘀膠囊（Fuzheng Huayu capsules，FHC）是国家食品药品监督管理局（CFDA）批准的抗肝纤维化中药产品，由虫草菌丝、丹参、桃仁、五味子、松黄粉及绞股蓝组成，针对慢性乙肝、肝炎后肝硬化正气（肝、脾、肾）虚损、血瘀阻络、湿热内留这一中医基本证候病机特点。该方可改善肝炎后肝硬化患者肝功能、调整异常免疫功能和降低血清肝纤维化标志物水平等，对乙肝肝纤维化的组织学逆转率达52%，且肝组织炎症活动度也有明显改善[1]。其作用机制包括抗脂质过氧化损伤、保护肝细胞炎性坏死与凋亡、调节转化生长因子（TGF）β1/Smads 信号通路与抑制肝星状细胞（HSC）活化、调节胞外基质代谢和抑制肝血管新生等[2]。……