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基于液相色谱-质谱代谢组学技术探索肝内胆汁淤积潜在血清代谢物标志物

[Exploring potential serum metabolite markers of intrahepatic cholestasis based on liquid chromatography-mass spectrometry metabolomics technology].

作者信息

Luo X, Li S X, Hai L, Liu S W, Ding X C, Liu X Y, Ma L N

机构信息

Department of Infectious Diseases, General Hospital of Ningxia Medical University, Yinchuan 750004, China.

College of Clinical Medical, Ningxia Medical University, Yinchuan 750004,China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2024 Aug 20;32(8):753-760. doi: 10.3760/cma.j.cn501113-20231030-00161.

DOI:10.3760/cma.j.cn501113-20231030-00161
PMID:39267570
Abstract

To analyze the blood differential metabolites of patients with intrahepatic cholestasis (IHC) by liquid chromatography-mass spectrometry metabolomics technology so as to find potential metabolic target. Serum samples were collected from thirty patients with intrahepatic cholestasis and thirty healthy individuals after metabolomics analysis. The differential metabolites were initially screened based on the multiple differences and significance. KEGG enrichment analysis was performed on the differential metabolites to determine the candidate targets. The potential clinical application value of these characteristic metabolites was analyzed using the receiver operating characteristic curve. A total of thirty patients with intrahepatic cholestasis and thirty healthy adults were included. The age difference between the two groups was not statistically significant (>0.05). The clinical condition was consistent with the statistically significant differences in liver biochemical indicators, blood routine, coagulation, and inflammatory indicators between the two groups (<0.05). Furthermore, a blood metabolomics screening analysis revealed 99 differentially expressed metabolites associated with intrahepatic cholestasis. Of these, 15 showed statistically significant differences. Glucose, lipid, and energy metabolisms were the various primary types of differential metabolites involved. The receiver operating characteristic curve>0.9 included the following twelve kinds of metabolites: 1H-indole-3-carboxaldehyde, 6-hydroxy-1H-indole-3-acetamide, phenylalanyl tryptophan, 1-methylguanosine, 2-ethoxy-5-methylpyrazine, p-hydroxybenzaldehyde, 5-(2-chlorophenyl)-3,4-dihydro-2H-pyrrole, methylthioadenosine, alanylisoleucine, anabsinthin, N-acetyl-DL-histidine monohydrate, N-methylnicotinamide, and others. The fifteen metabolites that were previously identified and calculated according to the differential quantitative value of the metabolite corresponding ratio exhibited fold-changes in the upregulated and downregulated potential biomarkers (phenylalanine tryptophan, phenylalanine, 5'-methylthioadenosine, anabsinthin, and N-methylnicotinamide) in combination with the area under the receiver operating characteristic curve>0.9. Phenylalanyl tryptophan, phenylalanylalanine, 5'-methylthioadenosine, anabsinthin, and N-methylnicotinamide may serve as potential metabolic markers to distinguish patients with cholestasis from healthy controls. N-methylnicotinamide, among them, is of great importance as a potential marker.

摘要

采用液相色谱 - 质谱代谢组学技术分析肝内胆汁淤积症(IHC)患者的血液差异代谢物,以寻找潜在的代谢靶点。代谢组学分析后,收集了30例肝内胆汁淤积症患者和30例健康个体的血清样本。基于多重差异和显著性初步筛选差异代谢物。对差异代谢物进行KEGG富集分析以确定候选靶点。使用受试者工作特征曲线分析这些特征性代谢物的潜在临床应用价值。共纳入30例肝内胆汁淤积症患者和30例健康成年人。两组年龄差异无统计学意义(>0.05)。两组在肝脏生化指标、血常规、凝血和炎症指标方面的临床情况存在统计学显著差异(<0.05)。此外,血液代谢组学筛查分析显示99种与肝内胆汁淤积相关的差异表达代谢物。其中15种显示出统计学显著差异。葡萄糖、脂质和能量代谢是涉及的主要差异代谢物类型。受试者工作特征曲线>0.9的包括以下12种代谢物:1H - 吲哚 - 3 - 甲醛、6 - 羟基 - 1H - 吲哚 - 3 - 乙酰胺、苯丙氨酰色氨酸、1 - 甲基鸟苷、2 - 乙氧基 - 5 - 甲基吡嗪、对羟基苯甲醛、5 -(2 - 氯苯基)- 3,4 - 二氢 - 2H - 吡咯、甲硫腺苷、丙氨酰异亮氨酸、苦艾素、N - 乙酰 - DL - 组氨酸一水合物、N - 甲基烟酰胺等。根据代谢物相应比例的差异定量值先前鉴定和计算的15种代谢物,结合受试者工作特征曲线下面积>0.9,在潜在生物标志物上调和下调方面表现出倍数变化(苯丙氨酰色氨酸、苯丙氨酸、5'-甲硫腺苷、苦艾素和N - 甲基烟酰胺)。苯丙氨酰色氨酸、苯丙氨酰丙氨酸、5'-甲硫腺苷、苦艾素和N - 甲基烟酰胺可作为区分胆汁淤积症患者与健康对照的潜在代谢标志物。其中,N - 甲基烟酰胺作为潜在标志物具有重要意义。

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