基于非靶向代谢组学软肝冲剂抗肝纤维化作用机制研究

Non-targeted Metabonomics of Ruangan Electuary(软肝冲剂)on CCl_4-induced Hepatic Fibrosis Rats

目的基于非靶向代谢组学探究软肝冲剂对CCl4所致大鼠肝纤维化的作用及其可能的作用机制。方法采用40%CCl4(2 mL·kg^(-1))诱导大鼠肝纤维化模型,每周2次,共计8周。造模第6周开始给与软肝冲剂,干预8周后采用HPLC-QTOF-MS联用技术检测软肝冲剂干预后各组大鼠血浆中代谢物的变化,利用Ropls软件进行偏最小二乘法判别分析(PLS-DA)、差异代谢物筛选及代谢通路分析。结果代谢组学分析显示,与模型组比较,软肝冲剂干预后共有137种代谢物发生变化,其中上调的有23种,下调的有114种,如异亮氨酸、鸟氨酸、酪氨酸、脱氧胆酸等。主要与氨基酸代谢、酪氨酸代谢、初级胆汁酸代谢等途径有关。结论软肝冲剂对CCl_(4)所致大鼠肝纤维化的治疗作用可能与调节氨基酸代谢、胆汁酸合成等代谢途径有关。

Objective Based on non-targeted metabonomics to explore the mechanism of Ruangan Electuary(软肝冲剂)against CCl_4-induced hepatic fibrosis in rats.Methods The rat hepatic fibrosis model was established by intragastric administration of 40%CCl_4(2 mL·kg^(-1)),twice a week,8 weeks in total.After the intervention of 6 weeks,Ruangan Electuary was given.After 8 weeks of intervention,HPLC-QTOF-MS combined technology was used to detect the changes of metabolites in the plasma of rats in each group.Ropls software was used for PLS-DA,differential metabolite screening and metabolic pathway analysis.Results Metabonomics analysis indicated that compared to the model control group,137 metabolites changed after the intervention of Ruangan Electuary,of which 23 were up-regulated and 114 were down-regulated,such as isoleucine,ornithine,m-tyrosine and deoxycholic acid 3-glucuronide and were mainly related to biosynthesis of amino acids,tyrosine metabolism and primary bile acid biosynthesis.Conclusion The therapeutic effect of Ruangan Electuary on CCl_(4)-induced hepatic fibrosis in rats may be related to the regulation of amino acid metabolism,bile acid synthesis and other metabolic pathways.