文献类型：期刊文献

中文题名：基于LC-MS/MS代谢组学技术探讨甘草缓解顺铂肝损伤的作用机制

英文题名：Exploring the mechanism of action of licorice in alleviating cisplatin liver injury based on LC-MS/MS metabolomics technology

作者：殷亭湄[1];杨必乾[1];付晓艳[1];高广淼[1];邓毅[1,2]

第一作者：殷亭湄

机构：[1]甘肃中医药大学,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

年份：2024

卷号：35

期号：9

起止页码：2067

中文期刊名：时珍国医国药

外文期刊名：Lishizhen Medicine and Materia Medica Research

收录：;北大核心:【北大核心2023】；CSCD:【CSCD_E2023_2024】；

基金：国家自然科学基金地区基金(81960723);甘肃省自然科学基金(21JR111RA145);甘肃省中医药管理局项目(GZKP-2022-37);甘肃省兰州市科技局项目(2022-3-21);甘肃省中药炮制技术传承基地项目。

语种：中文

中文关键词：甘草;顺铂;肝损伤;代谢组学;苯丙氨酸

外文关键词：Licorice;Cisplatin;Liver injury;Metabolomics;Phenylalanine

摘要：目的探究甘草对顺铂肝损伤缓解作用的作用机制。方法将48只SD大鼠随机分为空白组、模型组、阳性对照组和甘草组(450、900和1800 mg/kg)。给药第5天给药30 min后,模型组、阳性对照组和甘草组腹腔注射顺铂(8 mg/kg),建立急性肝损伤模型。采用LC-MS/MS非靶向代谢组学技术研究甘草缓解顺铂急性肝损伤的代谢产物和代谢途径。结果代谢组学样本的聚类在主成分分析图中显示出显著的分离,OPLS-DA模型中的三组在多变量统计分析中可以清楚地区分。在976种总代谢产物中,252种代谢产物在空白组和模型组之间存在显著差异,甘草能够调控其中33种差异代谢产物。将差异代谢物导入MetaboAnalyst 5.0数据库进行代谢通路分析,分析可知差异代谢产物主要参与淀粉和蔗糖代谢;半乳糖代谢;苯丙氨酸、酪氨酸和色氨酸的生物合成;酪氨酸代谢;cAMP信号通路;缬氨酸、亮氨酸和异亮氨酸的生物合成;缬氨酸、亮氨酸和异亮氨酸降解;氨基酸和核苷酸糖代谢等8条代谢通路。结论结果表明甘草对顺铂肝损伤缓解作用可能与其改善差异代谢物的水平,调节氨基酸代谢及糖代谢等有关通路密切相关。
Objective In order to study the mechanism of licorice's mitigating effect on cisplatin hepatic injury.Methods 48 SD rats were randomly divided into the blank group,the model group,the positive control group,and the licorice group(450,900,and 1800 mg/kg).Thirty minutes after administration on day 5,cisplatin(8 mg/kg)was intraperitoneally injected into the mod-el,positive control and licorice groups to establish an acute liver injury model.The metabolites and metabolic pathways of licorice to alleviate cisplatin acute liver injury were investigated using LC-MS/MS untargeted metabolomics.Results The clustering of metabolomics samples showed significant separation in principal component analysis plots,and the three groups in the OPLS-DA model could be clearly distinguished in multivariate statistical analysis.Of the 976 total metabolites,252 metabolites differed sig-nificantly between the blank and model groups,and licorice was able to modulate 33 of these differential metabolites.The differ-ential metabolites were imported into the MetaboAnalyst 5.0 database for metabolic pathway analysis,which revealed that the dif-ferential metabolites were mainly involved in metabolic pathways such as Starch and sucrose metabolism;Galactose metabolism;Phenylalanine,tyrosine and tryptophan biosynthesis;Tyrosine metabolism;cAMP signaling pathway;Valine,leucine and isoleu-cine biosynthesis;Valine,leucine and isoleucine degradation;Amino sugar and nucleotide sugar metabolism.Conclusion The results suggest that the mitigating effect of licorice on cisplatin liver injury may be closely related to its improvement in the levels of differential metabolites and regulation of amino acid metabolism and glucose metabolism and other related pathways.