文献类型：期刊文献

中文题名：基于非靶向代谢组学研究甘草对顺铂诱导肝损伤大鼠的保护作用

英文题名：The protective effect of licorice on cisplatin-induced liver injury in ratsbased on untargeted metabolomics study

作者：殷亭湄[1];杨必乾[1];高广淼[1];付晓艳[1];连小龙[2];杨玲玲[1];李洁[1];邓毅[1,3]

第一作者：殷亭湄

机构：[1]甘肃中医药大学药学院,甘肃兰州730000;[2]青海大学基础医学部,青海西宁810000;[3]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：2024

卷号：40

期号：12

起止页码：2246

中文期刊名：中国药理学通报

外文期刊名：Chinese Pharmacological Bulletin

收录：CSTPCD;;Scopus;北大核心:【北大核心2023】；CSCD:【CSCD2023_2024】；

基金：国家自然科学基金地区基金资助项目(No 81960723);甘肃省自然科学基金资助项目(No 21JR111RA145);甘肃省优秀博士生项目(No 22JR5RA577)。

语种：中文

中文关键词：甘草;顺铂;肝损伤;作用机制;代谢组学;氨基酸代谢

外文关键词：licorice;cisplatin;liver injury;mechanism of action;metabolomics;amino acid metabolism

摘要：目的 研究甘草对顺铂诱导肝损伤大鼠的保护作用及机制。方法 将48只SD大鼠随机分为空白组、模型组、阳性对照组以及甘草给药组(450、900和1 800 mg·kg^(-1))。预防性给药5 d后,对模型组、阳性对照组以及甘草给药组腹腔注射8 mg·kg^(-1)顺铂以建立急性肝损伤模型。采用LC-MS/MS非靶向代谢组学分析甘草缓解顺铂急性肝损伤的差异代谢物及代谢途径。结果 PLS-DA得分图显示代谢组学样本明显分离。分析得到1 19个与顺铂肝损伤相关的差异代谢物,其中31种差异代谢物在甘草干预后明显回调,主要参与D-精氨酸和D-鸟氨酸代谢;甲状旁腺激素的合成、分泌和作用;酪氨酸代谢;苯丙氨酸、酪氨酸和色氨酸的生物合成;β-丙氨酸代谢;氨基酸和核苷酸糖代谢。结论 代谢组学分析结果表明甘草可以改变顺铂致肝损伤大鼠代谢轮廓,分析其作用机制可能与改善差异代谢物的水平,参与调节机体氨基酸代谢等相关通路有关。
Aim To study the mechanism of action of licorice in alleviating cisplatin liver injury.Methods Forty-eight SD rats were randomly divided into a blank group,a model group,a positive control group and licorice administration groups(450,900 and 1800 mg·kg^(-1)).After 5 days of prophylactic administration,8 mg·kg^(-1) of cisplatin was injected intraperitoneally into the model,positive control,and licorice administration groups to establish an acute liver injury model.LC-MS/MS untargeted metabolomics was used to analyze the differential metabolites and metabolic pathways of licorice to alleviate cisplatin acute liver injury.Results PLS-DA score plots showed significant separation of metabolomics samples.The analysis yielded 119 differential metabolites associated with cisplatin liver injury,of which 31 differential metabolites were significantly regressed after licorice intervention and were mainly involved in D-arginine and D-ornithine metabolism;parathyroid hormone synthesis,secretion,and action;tyrosine metabolism;biosynthesis of phenylalanine,tyrosine,and tryptophan;β-alanine metabolism;and amino acid and nucleotide sugar metabolism.Conclusions Metabolomics analysis indicates that licorice can alter the metabolic profile of cisplatin-induced hepatic injury rats,and its mechanism of action may be related to its improvement of the levels of differential metabolites and its involvement in the regulation of amino acid metabolism and other related pathways.