基于LC-MS技术的二氢丹参酮Ⅰ抗肝纤维化肝脏代谢组学研究

Metabolomics study of dihydrotanshinoneⅠon hepatic fibrosis with LC-MS technology

目的利用肝脏代谢组学方法监测肝纤维化相关的代谢变化,评价二氢丹参酮Ⅰ治疗肝纤维化的药效及作用机制。方法将28只雄性SD大鼠随机分为4组:正常组、肝纤维化模型组和二氢丹参酮Ⅰ低剂量组、二氢丹参酮Ⅰ高剂量组。采用硫代乙酰胺诱导肝纤维化模型,给予4周治疗后,取大鼠肝脏进行液相色谱-质谱分析,结合OPLS-DA模式识别方法筛选模型组和正常组之间的差异代谢物,并以此评价二氢丹参酮Ⅰ对肝纤维化的治疗作用。结果通过肝脏代谢组学分析鉴定了38种肝纤维化相关的生物标志物,涉及谷胱甘肽代谢、褪黑素代谢、氨基酸代谢、脂质代谢、三羧酸循环等代谢通路,同时数据显示二氢丹参酮Ⅰ的干预对肝纤维化有改善作用。结论二氢丹参酮Ⅰ能够通过调节失衡的谷胱甘肽代谢、褪黑素代谢、氨基酸代谢、脂质代谢、三羧酸循环等途径而发挥预防和治疗肝纤维化作用。

Objective To evaluate therapeutic effects of dihydrotanshinoneⅠon hepatic fibrosis based on liver metabolomics method.Methods 28 rats were randomly divided into four groups including control group,hepatic fibrosis model group and dihydrotanshinoneⅠlow dose group and dihydrotanshinoneⅠhigh dose group.The dihydrotanshinoneⅠtreated groups received dihydrotanshinoneⅠfor 28 days.The rat liver samples were collected and analyzed by liquid chromatography-mass spectrometer(LC-MS).The OPLS-DA pattern recognition analysis of metabolomics differences among the groups and therapeutic effects of dihydrotanshinoneⅠon hepatic fibrosis were evaluated.Results 38 metabolites were identified through liver metabolomics analysis.The possible mechanism of hepatic fibrosis was mainly involved glutathione metabolism,melatonin metabolism,amino acid metabolism,lipid metabolism and TCA cycle.The hepatic fibrosis induced by TAA was reversed by dihydrotanshinoneⅠ.Conclusion DihydrotanshinoneⅠprovided satisfactory therapeutical effects on hepatic fibrosis through partially regulating the perturbed glutathione metabolism,melatonin metabolism,amino acid metabolism,lipid metabolism,TCA cycle.