基于代谢组学的补骨脂致特异质肝损伤机制研究

doi:10.19803/j.1672-8629.2021.11.04

中国药物警戒 ›› 2021, Vol. 18 ›› Issue (11): 1014-1019.
DOI: 10.19803/j.1672-8629.2021.11.04

• 药物性肝损伤科学评价与防控专栏 • 上一篇下一篇

基于代谢组学的补骨脂致特异质肝损伤机制研究

王晓艳¹, 李伟霞^1,2, 张辉¹, 张明亮¹, 吴娅丽¹, 曹站霞¹, 泥文娟², 陈毓龙², 李琨², 冯科冉², 唐进法^1,2,*

¹河南中医药大学第一附属医院中药临床评价技术河南省工程实验室,河南郑州 450000;
²河南中医药大学药学院,河南郑州 450008

收稿日期:2021-04-21 发布日期:2021-11-18
通讯作者: ^*唐进法,男,博士,主任药师,中药质量评价与临床合理用药。E-mail：a0519@163.com
作者简介:王晓艳,女,博士,主管药师,中药学。
基金资助:
国家自然科学基金资助项目（U1904129）; 河南省高等学校重点科研项目计划（19A360007）; 河南省中医药科学研究专项重点课题（2019ZYBJ08）; 河南省自然科学基金（212300410188）; 河南省中医药科学研究专项课题（2017ZY2019,2016ZY2057）; 河南中医药大学科研苗圃工程项目（MP2017-11）; 河南省中医药拔尖人才培养项目

The Mechanism of Psoralea Fructus Induced Idiosyncratic Liver Injury Based on Metabolomics

WANG Xiaoyan¹, LI Weixia^1,2, ZHANG Hui¹, ZHANG Mingliang¹, WU Yali¹, CAO Zhanxia¹, NI Wenjuan², CHEN Yulong², LI Kun², FENG Keran², TANG Jinfa^1,2,*

¹Henan Engineering Laboratory for Clinical Evaluation Technology of Chinese Medicine, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou Henan 450000, China;
²School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou Henan 450008, China

Received:2021-04-21 Published:2021-11-18

摘要/Abstract

摘要： 目的从代谢组学层面探索补骨脂肝损伤机制,筛选相关生物标志物及代谢通路。方法采用尾静脉注射脂多糖（LPS）法建立特异质肝损伤模型,实验动物随机分为对照组（CMC组）、补骨脂组（BGZ组）、LPS组、BGZ+LPS组,检测血清谷丙转氨酶（ALT）和谷草转氨酶（AST）活性。通过UPLC-QTOF/MS分析不同组别大鼠血清样品的代谢轮廓谱,借助Progenesis QI（v2.4）、SIMCA v13.0等软件及MetaboAnalyst v5.0在线数据库,分析各组血清代谢标志物及其代谢通路。结果补骨脂单独给药对ALT和AST无明显影响,而联合LPS后ALT和AST显著升高,发生明显肝损伤。OPLS-DA结果显示,CMC、BGZ、LPS和BGZ+LPS组血清代谢物谱得到明显分离,筛选14个与补骨脂特异质肝损伤相关的潜在生物标志物,涉及17条代谢通路。结论补骨脂肝损伤为特异质肝损伤,其机制可能与调节鞘脂代谢、酪氨酸代谢等代谢途径相关。

关键词: 补骨脂, 特异质肝损伤, 代谢组学, 生物标志物, 代谢通路

Abstract: Objectiv eTo study the mechanism of Psoralea Fructus induced idiosyncratic injury based on metabolomics, and to screen related biomarkers and metabolic pathways. Methods A rat model of idiosyncratic liver injury was induced by caudal vein injection of LPS (LPS). Rats were randomly divided into the control group (CMC group), Psoralea Fructus group (BGZ group), lipopolysaccharide group and BGZ+LPS group. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were analyzed. Global metabolomics profiling of the serum was detected by UPLC-QTOF/MS. The characteristic biomarkers and corresponding metabolic pathways were analyzed by Progenesis QI (v2.4), SIMCA v13.0, MetaboAnalyst v 5.0 and other software. Results Compared with the control group, there were no significant changes in ALT or AST in the BGZ group, but there was an increase in ALT and AST in the BGZ+LPS group. Furthermore, serum metabolite spectra in the CMC, BGZ, LPS and BGZ+LPS groups were significantly separated from OPLS-DA. Fourteen potential metabolomics biomarkers were screened that were associated with Psoralea Fructus induced idiosyncratic injury, involving seventeen pathways. Conclusion Psoralea Fructus induced liver injury is idiosyncratic liver injury, and its mechanism is possibly related to the regulation of sphingolipid metabolism, tyrosine metabolism and other metabolic pathways.

Key words: Psoralea Fructus, idiosyncratic liver injury, metabolomics, biomarkers, metabolic pathway

中图分类号:

R917.1

王晓艳, 李伟霞, 张辉, 张明亮, 吴娅丽, 曹站霞, 泥文娟, 陈毓龙, 李琨, 冯科冉, 唐进法. 基于代谢组学的补骨脂致特异质肝损伤机制研究[J]. 中国药物警戒, 2021, 18(11): 1014-1019.

WANG Xiaoyan, LI Weixia, ZHANG Hui, ZHANG Mingliang, WU Yali, CAO Zhanxia, NI Wenjuan, CHEN Yulong, LI Kun, FENG Keran, TANG Jinfa. The Mechanism of Psoralea Fructus Induced Idiosyncratic Liver Injury Based on Metabolomics[J]. Chinese Journal of Pharmacovigilance, 2021, 18(11): 1014-1019.

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基于代谢组学的补骨脂致特异质肝损伤机制研究

The Mechanism of Psoralea Fructus Induced Idiosyncratic Liver Injury Based on Metabolomics

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