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GC-TOF-MS 分析血清代谢组学研究冬凌草甲素对 CCl 诱导的小鼠肝纤维化的保护作用。

Serum metabonomics study of the hepatoprotective effect of amarogentin on CCl-induced liver fibrosis in mice by GC-TOF-MS analysis.

机构信息

Department of Natural Medicine, School of Pharmacy, Fourth Military Medical University, 169 West Changle Road, Xi'an 710032, China.

Department of Pharmacy, the 456th Hospital of the People's Liberation Army, Jinan 250031,China.

出版信息

J Pharm Biomed Anal. 2018 Feb 5;149:120-127. doi: 10.1016/j.jpba.2017.10.029. Epub 2017 Oct 31.

Abstract

Amarogentin (AG) is a secoiridoid glycoside that is mainly extracted from the traditional Chinese medicine Swertia and Gentiana, which have been widely used in clinical practice to treat liver disease. However, the exact hepatoprotective mechanism of AG was still looking forward to further elucidation by far. In this study, C57BL/6 mice were divided into the following three groups: control, model and AG. Fibrosis was induced by CCl. Mice were orally treated with 100mg/kg AG or with normal saline as a control. At the end of the experiment, the validity of the model and the hepatoprotective effects of AG were examined by histopathology and biochemical indicators. Metabonomics technology was further performed to systematically evaluate the endogenous metabolite profiles. Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) technology with pattern recognition analysis, including principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA), showed a clear separation of the model group and the control group, with the AG treatment group located much closer to the control group than the model group, which was consistent with the results of biochemical and histopathological assays. Moreover, nine potential biomarkers were identified to elucidate the drug mechanism of AG, which may be related to pathways of amino acid and fatty acid metabolism.

摘要

獐芽菜苦苷(AG)是一种主要从传统中药獐牙菜和秦艽中提取的环烯醚萜苷类化合物,已广泛用于临床治疗肝脏疾病。然而,AG 的确切保肝机制仍有待进一步阐明。在这项研究中,C57BL/6 小鼠被分为以下三组:对照组、模型组和 AG 组。通过 CCl 诱导纤维化。用 100mg/kg AG 或生理盐水作为对照对小鼠进行口服治疗。在实验结束时,通过组织病理学和生化指标检查模型的有效性和 AG 的保肝作用。进一步采用代谢组学技术系统评估内源性代谢物图谱。气相色谱飞行时间质谱(GC-TOF-MS)技术结合模式识别分析,包括主成分分析(PCA)和正交偏最小二乘判别分析(OPLS-DA),显示模型组和对照组之间有明显的分离,AG 治疗组与对照组的距离比模型组更近,这与生化和组织病理学检测结果一致。此外,鉴定了 9 个潜在的生物标志物来阐明 AG 的药物作用机制,这可能与氨基酸和脂肪酸代谢途径有关。

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