京大戟醋制前后乙酸乙酯部位毒性与血清代谢组学差异研究  

Differences in toxicity and serum metabolomics of ethyl acetate fraction of Euphorbiae Pekinensis Radix before and after vinegar processing

作　　者：邵霞[1] 张丽[1] 曹雨诞[1] SHAO Xia;ZHANG Li;CAO Yu-dan(Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]南京中医药大学江苏省中药资源产业化过程协同创新中心/中药资源产业化与方剂创新药物国家地方联合工程研究中心,江苏南京210023

出　　处：《中国中药杂志》2024年第21期5888-5897,共10页China Journal of Chinese Materia Medica

基　　金：江苏省自然科学基金面上项目(BK20201232)。

摘　　要：研究京大戟醋制前后乙酸乙酯部位的毒性差异,并借助非靶向代谢组学探究其醋制减毒的作用机制。采用UFLC-Q-TOF-MS对京大戟醋制前后乙酸乙酯部位的萜类成分变化进行研究。正常大鼠灌胃给予生、醋京大戟乙酸乙酯部位,通过组织病理形态学观察,血清肝肾功能、氧化损伤、炎性损伤指标和细胞凋亡因子检测,评价京大戟醋制前后乙酸乙酯部位的毒性差异。利用血清代谢组学技术,寻找内源性代谢物的变化,通过主成分分析(PCA)和偏最小二乘判别分析(PLS-DA),寻找与京大戟醋制减毒相关的差异代谢物及代谢通路。京大戟醋制后乙酸乙酯部位的萜类成分含量大幅降低。组织病理切片和各指标结果表明京大戟醋制前后乙酸乙酯部位均能诱导肝、胃、肠毒性,其相关毒性与氧化损伤、炎性损伤、细胞凋亡有关,醋制后乙酸乙酯部位毒性降低。血清代谢组学筛选了13个差异代谢物,得到了5条主要代谢通路;由PCA和PLS-DA得分图可知,京大戟醋制前后乙酸乙酯部位均可造成大鼠体内内源性代谢谱的紊乱,主要集中在脂质代谢、原发性胆汁酸生物合成、花生四烯酸代谢等方面,醋制能缓解上述代谢紊乱。由此可知,京大戟乙酸乙酯部位确有肝、胃、肠毒性,醋制后萜类成分含量降低致其毒性下降,其作用机制可能与减轻氧化损伤、炎性损伤、细胞凋亡和改善脂质代谢有关。This study aimed to investigate the toxicity differences of the ethyl acetate fraction of Euphorbiae Pekinensis Radix before and after vinegar processing and explore the detoxification mechanism of vinegar processing using non-targeted metabolomics.The changes in terpenoid components in the ethyl acetate fraction before and after vinegar processing were analyzed using UFLC-Q-TOF-MS.Normal rats were orally administered the raw and vinegar-processed ethyl acetate fractions of Euphorbia Pekinensis Radix.The toxicity differences in ethyl acetate fractions of Euphorbia Pekinensis Radix before and after vinegar processing were evaluated by pathological morphology,serum liver and kidney function,oxidative damage,and inflammatory injury indicators,and apoptosis factors.Serum metabolomics technology was utilized to identify changes in endogenous metabolites.Principal component analysis(PCA)and partial least squares discriminant analysis(PLS-DA)were employed to identify differential metabolites and metabolic pathways related to the detoxification of vinegar-processed Euphorbia Pekinensis Radix.The content of terpenoid components in the ethyl acetate fraction of Euphorbia Pekinensis Radix significantly decreased after vinegar processing.Histopathological sections and various indicators revealed that both the raw and vinegar-processed ethyl acetate fractions of Euphorbia Pekinensis Radix could induce toxicity in the liver,stomach,and intestine,with a reduction after vinegar processing.The toxicity was associated with oxidative damage,inflammatory injury,and apoptosis.A total of 13 differential metabolites and 5 main metabolic pathways related to Euphorbia Pekinensis Radix toxicity were identified by serum metabolomics.PCA and PLS-DA score plots indicated that both the raw and vinegar-processed ethyl acetate fractions disrupted the endogenous metabolic profiles in rats,mainly concentrating on lipid metabolism,primary bile acid biosynthesis,and arachidonic acid metabolism,with vinegar processing alleviating these metabolic dis

关 键 词：京大戟乙酸乙酯部位 醋制 毒性 氧化损伤 炎性损伤 细胞凋亡 血清代谢组学 

分 类 号：R285.5[医药卫生—中药学]