文献类型：期刊文献

中文题名：西黄丸对乳腺增生大鼠干预的尿液代谢组学研究

英文题名：Urine metabolomics study of intervention of Xihuang Pills in rats with hyperplasia of mammary gland

作者：王婧瑞[1];陶蕊[1];马学莉[1];王俊亮[1];韩涛[1,2]

第一作者：王婧瑞

机构：[1]甘肃中医药大学药学院,甘肃兰州730000;[2]甘肃省中药药理与毒理学重点实验室,甘肃兰州730000

第一机构：甘肃中医药大学药学院（西北中藏药协同创新中心办公室）

年份：2023

卷号：48

期号：20

起止页码：5632

中文期刊名：中国中药杂志

外文期刊名：China Journal of Chinese Materia Medica

收录：CSTPCD;;Scopus;北大核心:【北大核心2020】；CSCD:【CSCD2023_2024】；PubMed;

基金：国家自然科学基金项目(82160853)。

语种：中文

中文关键词：西黄丸;乳腺增生;尿液代谢组学;UPLC-Q-Orbitrap-MS

外文关键词：Xihuang Pills;hyperplasia of mammary gland;urine metabolomics;UPLC-Q-Orbitrap-MS

摘要：基于高效液相色谱-四极杆-静电场轨道阱质谱法(UPLC-Q-Orbitrap-MS)的尿液代谢组学研究西黄丸改善乳腺增生(hyperplasia of mammary gland,HMG)大鼠的作用机制。肌肉注射苯甲酸雌二醇注射液0.5 mg·kg^(-1),连续25 d,然后肌肉注射黄体酮注射液5 mg·kg^(-1),连续5 d建立乳腺增生大鼠模型。利用UPLC-Q-Orbitrap-MS技术建立空白组、模型组和西黄丸组大鼠尿液样本中内源性小分子代谢轮廓谱。多元统计分析进行模式识别,t检验、变量投影重要性(variable importance in the projection,VIP)筛选潜在生物标志物,并结合HMDB在线数据库对显著变化的差异代谢物进行鉴定,MetaboAnalyst 5.0数据库富集代谢通路。结果表明,利用HMDB在线数据库指认出空白组与模型组大鼠之间有90个差异代谢物发生显著变化(P<0.05),其中有48种代谢物在西黄丸给药后显著回调(P<0.05),可能与西黄丸的调控作用有关;将差异代谢物导入MetaboAnalyst 5.0数据库进行代谢通路分析,共筛选到13条与乳腺增生显著相关的代谢通路,西黄丸能调节其中的7条。此代谢通路主要涉及组氨酸代谢,精氨酸和脯氨酸代谢,β-丙氨酸代谢,甘氨酸、丝氨酸和苏氨酸代谢,色氨酸代谢,嘧啶代谢,氨基糖和核苷酸糖代谢等代谢通路。该研究利用UPLC-Q-Orbitrap-MS和尿液代谢组学技术联合分析西黄丸改善HMG的作用机制,为进一步深入研究奠定基础。
This study aimed to investigate the mechanism of Xihuang Pills in improving hyperplasia of mammary gland(HMG) in rats based on urine metabolomics using ultra-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry(UPLC-Q-Orbitrap-MS).The HMG rat model was established by intramuscular injection of estradiol benzoate solution(0.5 mg·kg^(-1),25 days) followed by progesterone injection(5 mg·kg^(-1),5 days).UPLC-Q-Orbitrap-MS technology was used to establish the endogenous small-molecule metabolic profiles in urine samples of rats in the blank group,the HMG model group,and Xihuang Pills group.Multivariate statistical analysis was performed for pattern recognition,t test and variable importance in the projection(VIP) were used to screen potential biomarkers.The significantly changed differential metabolites were identified using the online database Human Metabolome Database(HMDB).Metabolic pathway enrichment analysis was conducted using the MetaboAnalyst 5.0 database.The results showed that 90 differential metabolites with significant changes(P<0.05) were identified between the blank group and the HMG model group using the HMDB.Among them,48 metabolites significantly reverted(P<0.05) after administration of Xihuang Pills,which may be related to the regulatory effect of Xihuang Pills.Thirteen metabolic pathways significantly associated with HMG were identified when the differential metabolites were imported into the MetaboAnalyst 5.0 database,and Xihuang Pills could modulate seven of these pathways.These metabolic pathways mainly involved histidine metabolism,arginine and proline metabolism,β-alanine metabolism,glycine,serine and threonine metabolism,tryptophan metabolism,pyrimidine metabolism,and amino sugar and nucleotide sugar metabolism.This study utilized UPLC-Q-Orbitrap-MS and urine metabolomics technology to analyze the mechanism of Xihuang Pills in improving HMG,laying the foundation for further in-depth research.