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基于葡聚糖硫酸钠诱导的急性结肠炎小鼠模型的肝脏代谢组学分析:肠-肝连接的意义。

Metabolomic Analysis of the Liver of a Dextran Sodium Sulfate-Induced Acute Colitis Mouse Model: Implications of the Gut-Liver Connection.

机构信息

Lab of Molecular Toxicology, College of Pharmacy, Pusan National University, Busan 46241, Korea.

Department of Chemistry, Center for Proteome Biophysics and Chemistry Institute for Functional Materials, Pusan National University, Busan 46241, Korea.

出版信息

Cells. 2020 Feb 1;9(2):341. doi: 10.3390/cells9020341.

Abstract

The incidence of ulcerative colitis (UC) is increasing worldwide, and it has become a growing problem in Asia. Previous research on UC has focused on serum, plasma, urine, gut tissues, and fecal metabolic profiling, but a comprehensive investigation into the correlation between the severity of colitis and changes in liver metabolism is still lacking. Since the liver and gut exchange nutrients and metabolites through a complex network, intestinal diseases can affect both the liver and other organs. In the present study, concentration-dependent dextran sodium sulfate (DSS)-induced ulcerative colitis was employed to examine changes in liver metabolism using a proton nuclear magnetic resonance spectroscopy (H-NMR)-and ultra-performance liquid chromatography time of flight mass spectroscopy (UPLC-TOF MS)-based metabolomics study. Using the multivariate statistical analysis method orthogonal projections to latent structures discriminant analysis (OPLS-DA), changes in metabolites depending on the DSS dose could be clearly distinguished. Specifically, hepatic metabolites involved in one-carbon metabolism, carnitine-related metabolism, and nucleotide synthesis were found to be affected by intestinal inflammation, implying the existence of a metabolic connection between the gut and liver. We are currently investigating the significance of this metabolic condition in UC.

摘要

溃疡性结肠炎(UC)的发病率在全球范围内呈上升趋势,在亚洲也成为了一个日益严重的问题。之前的 UC 研究主要集中在血清、血浆、尿液、肠道组织和粪便代谢物分析上,但对结肠炎严重程度与肝脏代谢变化之间的相关性仍缺乏全面的研究。由于肝脏和肠道通过复杂的网络交换营养物质和代谢物,肠道疾病会同时影响肝脏和其他器官。在本研究中,采用浓度依赖性葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎模型,通过基于质子核磁共振波谱(H-NMR)和超高效液相色谱飞行时间质谱(UPLC-TOF MS)的代谢组学研究,考察了肝脏代谢的变化。使用多元统计分析方法正交投影判别分析(OPLS-DA),可以清楚地区分DSS 剂量依赖性的代谢物变化。具体而言,涉及一碳代谢、肉碱相关代谢和核苷酸合成的肝代谢物受到肠道炎症的影响,这表明肠道和肝脏之间存在代谢联系。我们目前正在研究这种代谢状态在 UC 中的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f4c/7072179/8d8dac00c215/cells-09-00341-g001.jpg

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