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基于 UPLC/Q-TOFMS 的三七总皂苷对酒精性肝损伤保护作用的代谢组学研究。

UPLC/Q-TOFMS-Based Metabolomics Studies on the Protective Effect of Panax notoginseng Saponins on Alcoholic Liver Injury.

机构信息

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, P. R. China.

Waters Technologies (Shanghai) Ltd., Shanghai, P. R. China.

出版信息

Am J Chin Med. 2015;43(4):695-714. doi: 10.1142/S0192415X15500433. Epub 2015 Jul 1.

Abstract

Consistent, excessive alcohol consumption leads to liver injury. The aim of the present study is to evaluate the possible efficacy of Panax notoginseng saponins (PNS) against chronic alcohol-induced liver injury using LC-MS-based urinary metabolomics. Mice were fed a Lieber-DeCarli liquid diet containing alcohol or isocaloric maltose dextrin as a control diet with or without PNS (200 mg/kg/BW) for 4 weeks. Treatment with PNS significantly reduced the increases in plasma ALT and AST levels, hepatic levels of reactive oxygen species (ROS) and malondialdehyde (MDA), which induced by chronic alcohol exposure. Conversely, PNS was also found to restore the glutathione (GSH) depletion and increase the superoxide dismutase (SOD) activities. The end-point urine sample of each mouse was collected overnight (24 h) in metabolic cages and their metabolic profiling changes were analyzed using UPLC/Q-TOFMS followed by multivariate statistical analysis. After 4 week of Lieber-DeCarli alcohol diet feeding, the metabolic profile experienced great perturbation in PCA score plot, and the treatment of PNS could assist to regulate the disturbed metabolic profile induced by alcohol exposure. Additionally, sixteen potential biomarkers responsible for derivations of the metabolic profile induced by alcohol exposure were identified, and the alcohol-induced changes in these biomarkers, except hexanoylglycine, could be partially or nearly reversed by PNS treatment. Taken together, PNS protects against chronic alcohol-induced liver injury. Our findings demonstrated that the LC-MS-based metabolomics approach is a useful tool to investigate the efficacy of Chinese medicines.

摘要

持续过量饮酒会导致肝损伤。本研究旨在采用基于 LC-MS 的尿代谢组学方法评估三七总皂苷(PNS)对慢性酒精性肝损伤的可能疗效。将小鼠用含有酒精的 Lieber-DeCarli 液体饮食或等热量麦芽糊精作为对照饮食喂养,同时给予或不给予 PNS(200mg/kg/BW)4 周。PNS 治疗可显著降低慢性酒精暴露引起的血浆 ALT 和 AST 水平、肝内活性氧(ROS)和丙二醛(MDA)水平的升高。相反,PNS 还被发现可恢复谷胱甘肽(GSH)耗竭并增加超氧化物歧化酶(SOD)活性。将每只小鼠的终点尿样在代谢笼中收集过夜(24 小时),并用 UPLC/Q-TOFMS 进行代谢组学分析,然后进行多变量统计分析。经过 4 周的 Lieber-DeCarli 酒精饮食喂养,PCA 得分图显示代谢谱发生了很大的扰动,PNS 的治疗可以帮助调节酒精暴露引起的代谢谱紊乱。此外,鉴定出 16 个与酒精暴露引起的代谢谱变化相关的潜在生物标志物,除己酰甘氨酸外,PNS 治疗可部分或几乎逆转这些生物标志物的变化。总之,PNS 可预防慢性酒精性肝损伤。我们的研究结果表明,基于 LC-MS 的代谢组学方法是研究中药疗效的有用工具。

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