何首乌致肝损伤大鼠的动态血清代谢组学研究

Dynamic serum metabolomics study of liver injury in rats caused by Polygonum multifulorum

该文采用液相色谱-质谱方法测定服用何首乌大鼠的血清代谢指纹谱,同时利用多元统计分析方法比较代谢谱差异并筛查显著相关的生物标志物,考察其动态变化趋势。探讨何首乌致大鼠肝脏损伤的代谢组学动态变化,寻找其显著相关的生物标志物,并考察标志物的动态变化趋势,以期为何首乌致肝损伤的内在机制与临床早期诊断提供依据。结果显示给药后不同时间点大鼠的血清代谢轮廓存在一定的差异,经比较分析,共筛选得到6个潜在生物标志物:oleamide,lyso PC(16∶0),leukotriene A4,trans-tetra-dec-2-enoic acid,dihydrocortisol和7a-hydroxydehydroepiandrosterone,这些标志物在何首乌致肝损伤动态过程中呈现一定的变化趋势。所筛选到的生物标志物在给药1周后含量即出现明显变化,相比于ALT,AST来说更加敏感。一定程度上可揭示出何首乌造成肝损伤的动态机制以及肝脏自我修复表现,对于监测服用何首乌患者肝功能、早期发现何首乌肝损伤具有潜在的应用价值和意义。

Liquid chromatography-mass spectrometry method was used for determination of metabolic fingerprint spectrum in rat ser- um, and the method of multivariate statistical analysis was used to compare the metabolism spectrum difference and screen significantly related biomarkers. The dynamic change trend was investigated at the same time. The dynamic metabonomics changes of liver injury in rats caused by Polygonum multifulorum（PM） were investigated; significantly related biomarkers were found and their dynamic change trend was investigated to provide basis for internal mechanism and early clinical diagnosis. There was certain difference in serum meta- bolic profile of the rats at different time points. Six potential biomarkers were screened through comparative analysis, including oleam- ide, lysoPC（ 16： 0）, leukotriene A4, trans-tetra-dec-2-enoic acid, dihydrocortisol and 7a-hydroxydehydroepiandrosterone. These mark- ers presented the dynamic change trend in the process of PM causing liver damage. The biomarkers contents had a significant change after one week of drug administration, more sensitive than ALT and AST. It can reveal the dynamic mechanism of PM causing liver damage and hepatic self-healing performance to some extent, with important application value and significance for monitoring liver func- tion and early detecting diagnosis for patients with PM.