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
投稿时间:2021-01-30  修订日期:2021-07-20  点此下载全文
引用本文:陶朝阳,朱臻宇,邢心睿,曹奇,王辉.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[J].药学实践杂志,2021,39(5):403~408,471
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作者单位E-mail
陶朝阳 西藏军区总医院药物制剂研究中心西藏 拉萨 850071  
朱臻宇 海军军医大学药学院上海 200433  
邢心睿 海军军医大学药学院上海 200433  
曹奇 海军军医大学药学院上海 200433  
王辉 海军军医大学药学院上海 200433 wanghuiuuh@163.com 
基金项目:国家自然科学基金(81773683)
中文摘要: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。
中文关键词:肝纤维化  二氢丹参酮Ⅰ  液相色谱-质谱联用  代谢组学
 
Metabolomics study of dihydrotanshinone on hepatic fibrosis with LC-MS technology
Abstract:Objective To evaluate therapeutic effects of dihydrotanshinone Ⅰ on hepatic fibrosis based on liver metabolomics method.Methods 28 rats were randomly divided into four groups including control group, hepatic fibrosis model group and dihydrotanshinone Ⅰ low dose group and dihydrotanshinone Ⅰ high dose group. The dihydrotanshinone Ⅰ treated groups received dihydrotanshinone Ⅰ for 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 dihydrotanshinone Ⅰ on 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 dihydrotanshinone Ⅰ.Conclusion Dihydrotanshinone Ⅰ provided satisfactory therapeutical effects on hepatic fibrosis through partially regulating the perturbed glutathione metabolism, melatonin metabolism, amino acid metabolism, lipid metabolism, TCA cycle.
keywords:hepatic fibrosis  dihydrotanshinone I  LC-MS  metabolomics
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