Page 45 - 《中国药房》2023年4期

甘遂醋炙减毒机制的主要途径及靶点预测
Δ

＊
杨晓旭 ，贺志敏，李文兰（哈尔滨商业大学药学院，哈尔滨 150001）
#
中图分类号 R917；R285 文献标志码 A 文章编号 1001-0408（2023）04-0423-06
DOI 10.6039/j.issn.1001-0408.2023.04.08

摘 要 目的 研究甘遂醋炙减毒机制的主要途径及靶点。方法 取 24 只 SPF 级 SD 大鼠，随机分为空白组、生甘遂组（850
mg/kg）、醋甘遂组（850 mg/kg），每组8只。空白组灌胃0.5%羧甲基纤维素钠溶液，生甘遂组、醋甘遂组给予相应的供试品药液，连
续给药20 d，第20天收集大鼠12 h尿液。采用超高效液相色谱串联四极杆静电场轨道阱高分辨质谱（UPLC-Q-Exactive-MS）技术
分析尿液样本。经Compound Discoverer 3.0软件进行数据前处理，经BioCyc、HMDB等数据库进行代谢物结构鉴定，应用主成分
分析（PCA）、正交偏最小二乘法-判别分析（OPLS-DA）等多种方法观察不同组别是否呈现各自聚类现象；基于MetaboAnalyst进行
通路分析，对甘遂醋炙减毒机制潜在靶点进行预测。结果 鉴定出20个有显著性差异的内源性代谢物，其中有N-乙酰基-L-天冬
氨酸、3-磷酸羟基丙酮酸等10个目标生物标志物为醋甘遂减毒机制作用靶点，参与的主要代谢通路包括精氨酸生物合成，丙氨酸、
天冬氨酸和谷氨酸代谢，半胱氨酸和蛋氨酸代谢及精氨酸和D-鸟氨酸代谢。对通路中所有相关代谢物的生物学意义进行分析推
测，甘遂醋炙后可能通过降低N-乙酰基-L-天冬氨酸水平缓解神经毒性，通过升高L-高精氨酸水平对心脑血管系统存在保护作用
等。结论 甘遂经醋炙后，可对机体的神经系统、心脑血管系统、免疫系统及能量代谢等方面的不利因素有明显改善，其发挥减毒
机制的最集中相关的代谢通路为精氨酸生物合成。
关键词 甘遂；炮制减毒；代谢组学；目标生物标志物；代谢通路

Main ways and target prediction of detoxification mechanism of Euphorbia kansui after stir-frying with
vinegar
YANG Xiaoxu，HE Zhimin，LI Wenlan（School of Pharmacy， Harbin University of Commerce， Harbin 150001，
China）

ABSTRACT OBJECTIVE To study main way and target of Euphorbia kansui after stir-frying with vinegar. METHODS
Twenty-four SPF grade SD rats were randomly divided into blank group， E. kansui group （850 mg/kg） and vinegar stir-fried E.
kansui group （850 mg/kg）， with 8 rats in each group. Blank group was given 0.5% sodium carboxymethyl cellulose solution
intragastrically， and E. kansui group and vinegar stir-fried E. kansui group were given relevant test sample for consecutive 20 d.
The rats’ urine of 12 hours was collected on the 20th day. The urine samples of rats in each group were determined by UPLC-Q-
Exactive-MS. The data was pre-processed by Compound Discoverer 3.0 software， and the metabolite structure was identified by
BioCyc， HMDB and other databases. Whether different groups presented their own clustering phenomenon was observed by
principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA）， etc. Based on the
pathway analysis of MetaboAnalyst， the potential targets of detoxification mechanism of E. kansui after stir-frying with vinegar
were predicted. RESULTS Twenty significantly differential endogenous metabolites were identified， of which 10 target metabolites，
such as N-acetyl-L-aspartate and 3-phosphonooxypyruvic acid， were targets of detoxification mechanism of E. kansui after stir-
frying with vinegar. The main metabolic pathways included arginine biosynthesis， alanine， aspartic acid and glutamic acid
metabolism， cysteine and methionine metabolism， and arginine and D-ornithine metabolism. The biological significance of all
related metabolites in the pathways was analyzed and speculated； after stir-frying with vinegar， E. kansui may alleviate
neurotoxicity by reducing the level of N-acetyl-L-aspartic acid； E. kansui had a protective effect on cardio-cerebrovascular system
by increasing the level of L-high arginine. CONCLUSIONS After stir-frying with vinegar， E. kansui can significantly improve the
adverse factors in terms of nervous system， cardio-cerebrovascular system， immune system and energy metabolism. The most
concentrated metabolic pathway related to its detoxification mechanism is arginine biosynthesis.
KEYWORDS Euphorbia kansui； processing and detoxification； metabonomics； target biomarkers； metabolic pathway

Δ 基金项目 黑 龙 江 省 重 点 研 发 计 划 指 导 类 项 目（No. 甘遂是大戟科植物甘遂 Euphorbia kansui T.N.Liou
GZ20210092） ex T.P.Wang 的干燥块根，具有良好的泻水逐饮、消肿散
＊第一作者 讲师，博士。研究方向：中药药效物质基础。E-mail： 结的功效 ，同时也具有严重的毒副作用，在临床中多以
[1]
africa5566@163.com
炮制品入药，其毒性反应表现为肝脏氧化损伤，心脏毒
# 通信作者 教授，博士生导师，博士。研究方向：中药药效物质基
[2]
础。E-mail：lwldzd@163.com 性，肠道毒性，皮肤、口腔黏膜刺激 等。研究表明，甘遂

中国药房 2023年第34卷第4期 China Pharmacy 2023 Vol. 34 No. 4 · 423 ·