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基于超高效液相色谱-四极杆/飞行时间质谱联用技术和网络药理学方法的血浆和胆汁综合代谢组学,以探索对急性酒精性肝损伤的潜在保护机制。

Integrated Plasma and Bile Metabolomics Based on an UHPLC-Q/TOF-MS and Network Pharmacology Approach to Explore the Potential Mechanism of -Protection From Acute Alcoholic Liver Injury.

作者信息

Su Lianlin, Mao Jing, Hao Min, Lu Tulin, Mao Chunqin, Ji De, Tong Huangjin, Fei Chenghao

机构信息

College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.

Nanjing University of Chinese Medicine, The Key Laboratory of Chinese Herbal Medicine Processing of Jiangsu Province, Nanjing, China.

出版信息

Front Pharmacol. 2020 Jan 16;10:1543. doi: 10.3389/fphar.2019.01543. eCollection 2019.

DOI:10.3389/fphar.2019.01543
PMID:32009955
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6975200/
Abstract

(SC) is a well-known important traditional Chinese medicine (TCM) that has been used to treat liver disease in China for a long time. However, its overall effects and mechanism of action are unclear. The present study aimed to explore the potential mechanism of SC in protection against alcoholic liver injury (ALI). In this research, to enable a full assessment of metabolic changes in ALI in Sprague-Dawley rats and to increase our understanding of physiological changes in normal and pathological states, ultra-high performance liquid chromatography combined with quadrupole time of flight mass spectrometry (UHPLC-Q/TOF-MS) was used to probe potential biomarkers to learn more about ALI and to evaluate the overall effect of SC for ALI in rats. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to investigate global metabolomic alterations and to evaluate the therapeutic effects of SC in rats. The component-target-pathway network of SC was then constructed on the basis of the network pharmacology, and the liver injury-relevant signaling pathways were thus dissected and validated. The results showed that SC has conspicuous therapeutic efficacy for ALI, as suggested by the results of the pathological section and biochemical index assays, such as those for Alanine aminotransferase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (AKP), γ-glutamyl transferase (γ-GT/GGT), Reactive oxygen species (ROS), and Malondialdehyde (MDA). Furthermore, 21 kinds of potential biomarkers were identified in plasma samples of ALI rats, and 20 kinds of potential biomarkers were identified in their bile samples. The biomarkers were mainly related to inflammation and dysfunctions of amino acids and energy metabolism. The recovery of these dysfunctions partly led to the curative effect of SC on ALI.

摘要

丹参(SC)是一种著名的重要传统中药,在中国长期用于治疗肝脏疾病。然而,其整体疗效和作用机制尚不清楚。本研究旨在探讨丹参保护酒精性肝损伤(ALI)的潜在机制。在本研究中,为了全面评估Sprague-Dawley大鼠ALI的代谢变化,并增进我们对正常和病理状态下生理变化的理解,采用超高效液相色谱结合四极杆飞行时间质谱(UHPLC-Q/TOF-MS)来探测潜在生物标志物,以更多地了解ALI,并评估丹参对大鼠ALI的整体效果。主成分分析(PCA)和正交偏最小二乘判别分析(OPLS-DA)用于研究整体代谢组学变化,并评估丹参对大鼠的治疗效果。然后基于网络药理学构建丹参的成分-靶点-通路网络,从而剖析和验证与肝损伤相关的信号通路。结果表明,病理切片和生化指标检测结果(如丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(AKP)、γ-谷氨酰转移酶(γ-GT/GGT)、活性氧(ROS)和丙二醛(MDA))表明,丹参对ALI具有显著的治疗效果。此外,在ALI大鼠的血浆样本中鉴定出21种潜在生物标志物,在其胆汁样本中鉴定出20种潜在生物标志物。这些生物标志物主要与炎症以及氨基酸和能量代谢功能障碍有关。这些功能障碍的恢复部分导致了丹参对ALI的治疗效果。

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