Wu Xiaofang, Zhang Yating, Qiu Jiaqi, Xu Ya, Zhang Jing, Huang Juan, Bai Junqi, Huang Zhihai, Qiu Xiaohui, Xu Wen
The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, China.
Key Laboratory of Quality Evaluation of Chinese Medicine of the Guangdong Provincial Medical Products Administration, Guangzhou, China.
Front Pharmacol. 2020 Dec 21;11:569144. doi: 10.3389/fphar.2020.569144. eCollection 2020.
The root of (Thunb.) Moldenke (syn.: Thunb., HSW) is a distinguished herb that has been popularly used in traditional Chinese medicine (TCM). Evidence of its potential side effect on liver injury has accumulated and received much attention. The objective of this study was to profile the metabolic characteristics of lipids in injured liver of rats induced by HSW and to find out potential lipid biomarkers of toxic consequence. A lipopolysaccharide (LPS)-induced rat model of idiosyncratic drug-induced liver injury (IDILI) was constructed and evident liver injury caused by HSW was confirmed based on the combination of biochemical, morphological, and functional tests. A lipidomics method was developed for the first time to investigate the alteration of lipid metabolism in HSW-induced IDILI rat liver by using ultra-high-performance liquid chromatography/Q-exactive Orbitrap mass spectrometry coupled with multivariate analysis. A total of 202 characterized lipids, including phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), sphingomyelin (SM), phosphatidylinositol (PI), lysophosphatidylinositol (LPI), phosphatidylserine (PS), phosphoglycerols (PG), and ceramide (Cer), were compared among groups of LPS and LPS + HSW. A total of 14 out 26 LPC, 22 out of 47 PC, 19 out of 29 LPE, 16 out of 36 PE, and 10 out of 15 PI species were increased in HSW-treated rat liver, which indicated that HSW may cause liver damage via interfering the phospholipid metabolism. The present work may assist lipid biomarker development of HSW-induced DILI and it also provide new insights into the relationships between phospholipid perturbation and herbal-induced idiosyncratic DILI.
（千金藤属植物）千金藤（学名：Stephania japonica (Thunb.) Moldenke，异名：Stephania sinica Diels、Stephania hernandifolia (Willd.) Walp.）的根是一种著名的草药，在传统中医中广泛应用。其对肝损伤潜在副作用的证据不断积累并受到广泛关注。本研究的目的是剖析千金藤诱导的大鼠肝损伤中脂质的代谢特征，并找出毒性后果的潜在脂质生物标志物。构建了脂多糖（LPS）诱导的特异质性药物性肝损伤（IDILI）大鼠模型，并通过生化、形态学和功能测试相结合的方法证实了千金藤所致的明显肝损伤。首次开发了一种脂质组学方法，通过超高效液相色谱/Q-Exactive轨道阱质谱联用多变量分析，研究千金藤诱导的IDILI大鼠肝脏中脂质代谢的变化。在LPS组和LPS + 千金藤组之间比较了总共202种已鉴定的脂质，包括磷脂酰胆碱（PC）、溶血磷脂酰胆碱（LPC）、磷脂酰乙醇胺（PE）、溶血磷脂酰乙醇胺（LPE）、鞘磷脂（SM）、磷脂酰肌醇（PI）、溶血磷脂酰肌醇（LPI）、磷脂酰丝氨酸（PS）、磷酸甘油（PG）和神经酰胺（Cer）。在千金藤处理的大鼠肝脏中，26种LPC中的14种、47种PC中的22种、29种LPE中的19种、36种PE中的16种以及15种PI中的10种含量增加，这表明千金藤可能通过干扰磷脂代谢导致肝损伤。本研究可能有助于千金藤诱导的药物性肝损伤的脂质生物标志物开发，也为磷脂紊乱与草药诱导的特异质性药物性肝损伤之间的关系提供了新的见解。
