扶正消瘤颗粒治疗原发性肝癌的疗效观察及血清代谢组学分析

Curative effect of fuzheng xiaoliu granules in the treatment of primary liver cancer and analysis of serum metabolomics

目的:观察扶正消瘤颗粒治疗Ⅱ期原发性肝癌的临床疗效及从代谢组学角度初步探讨其作用机制。方法:纳入60例经综合介入治疗后达完全缓解(CR)的Ⅱ期原发性肝癌患者,随机分为治疗组和安慰剂组各30例,服药1年,观察1年,比较两组1年复发率及中医证候积分、甲胎蛋白和肝功能分级变化。应用超高液相色谱质谱技术筛选两组治疗前后血清差异代谢物,分析代谢通路及相关生物学通路。结果:治疗组1年复发率显著低于安慰剂组、中医证候积分总体改善率明显优于安慰剂组(P<0.05),两组治疗后甲胎蛋白和肝功能分级对比差异无统计学意义(P>0.05)。代谢组学结果显示:治疗组治疗前后对比以及两组治疗后对比分别存在39、33种差异代谢物,对差异代谢物进行富集分析和拓扑分析后发现扶正消瘤颗粒可影响氨基酸代谢、脂肪酸代谢和嘌呤代谢等代谢通路。治疗组治疗前后对比与两组治疗后对比结果中的相同差异代谢物和代谢通路,FOLD CHANGE>1的相同差异代谢物包括硬脂酸、次黄嘌呤、犬尿酸、花生四烯酸、花生四烯酰多巴胺,Impact>0.1的相同代谢通路有花生四烯酸代谢和组氨酸代谢。结论:扶正消瘤颗粒可有效降低综合介入术后Ⅱ期肝癌患者的复发率、改善中医证候,可能通过调节参与氨基酸和脂肪酸等代谢通路的代谢物含量,抑制PI3K/Akt和ERK信号通路的激活从而发挥延缓肿瘤复发的作用。

AIM:To observe the clinical efficacy of Fuzheng Xiaoliu Granules in the treatment of stage II primary liver cancer and to explore its mechanism of action from the perspective of metabolomics.METHODS:Sixty patients with stage II primary liver cancer who achieved complete remission(CR)after comprehensive interventional therapy were randomly divided into treatment group and placebo group,with 30 patients in each group.They were treated for one year and observed for one year.The one-year recurrence rate,traditional chinese medicine(TCM)syndrome score,alpha-fetoprotein and child-pugh grade were compared between the two groups.The serum metabolites of the two groups before and after treatment were screened by ultra-high liquid chromatography-mass spectrometry technology,and the metabolic pathways and related biological pathways were analyzed.RESULTS:The one-year recurrence rate of the treatment group was significantly lower than that of the placebo group,and the overall improvement rate of TCM syndrome score was significantly better than that of the placebo group(P<0.05).There was no statistical significance in the comparison of alpha-fetoprotein and child-pugh grade between the two groups after treatment(P>0.05).Metabolomics results showed that there were 39 and 33 different metabolites in the treatment group before and after treatment and in the two groups after treatment,respectively.After enrichment analysis and topological analysis of the different metabolites,it was found that Fuzheng Xiaoliu Granules could affect amino acid metabolism,fatty acid metabolism and purine metabolism and other metabolic pathways.Before and after treatment in the treatment group and after treatment in the two groups,there were the same differential metabolites and metabolic pathways in the two comparison results.The same differential metabolites with FOLD CHANGE>1 include Stearic acid,Hypoxanthine,Kynurenic acid,Arachidonic acid,and NArachidonoyl Dopamine.The same metabolic pathways with Impact>0.1 include Arachidonic acid metabolism and Histidine metabolism.CONCLUSION:Fuzheng xiaoliu granules can effectively reduce the recurrence rate of stage II liver cancer patients after comprehensive intervention and improve the TCM syndrome.It may inhibit the activation of PI3K/Akt and ERK signaling pathways by regulating the content of metabolites involved in metabolic pathways such as amino acids and fatty acids,thereby delaying tumor recurrence.