摘要
目的:研究甘遂炮制前后对生理状态大鼠肝脏代谢组学的影响,探究醋制减毒机制。方法:取24只SPF级SD大鼠,随机分为空白组、生甘遂组、醋甘遂组,每组8只。空白组灌胃0.5%羧甲基纤维素钠(CMC-Na),生甘遂组、醋甘遂组给予相应的供试液,连续给药20 d,第20天收集肝脏。运用超高效液相色谱-四级杆-静电场轨道阱高分辨质谱(UPLC-Q-Exactive-MS)技术分析大鼠肝脏样本,通过Compound Discoverer 3.0软件进行数据前处理,检索HMDB等数据库。并对差异代谢物进行主成分分析(PCA)、正交偏最小二乘法-判别分析(OPLS-DA)、MetaboAnalyst对所得差异代谢物进行显著富集通路分析。结果:实验最终发现生甘遂组与空白组比对出具有生物学意义的28个差异代谢物,醋甘遂组与空白组比对出具有显著性差异的18个代谢物,其交集有13个代谢物。结论:通过生物学意义分析得到醋炙甘遂能够通过升高肝脏中牛磺脱氧胆酸和硬脂酰肉碱水平,降低早期脑损伤和2型糖尿病诱发的潜在风险;通过升高肝脏甘氨胆酸水平,促进调节机体免疫功能;通过升高肝脏20-羟基二十碳四烯酸水平,促进缺血性卒中后的神经血管重塑和功能恢复;通过升高肝脏3-羟基丁酸、油酰乙醇胺水平,发挥抗肿瘤、抗氧化和神经保护作用。其发挥减毒机制的相关代谢通路为花生四烯酸代谢、初级胆汁酸生物合成、酮体的合成与降解、牛磺酸和次牛磺酸代谢。
OBJECTIVE To explore the attenuation mechanism of vinegar through the metabolomic study on liver of rats in physiological state treated with Euphorbia kansui before and after processing.METHODS Twenty-four SPF SD rats were ran⁃domly divided into blank group,E.kansui group and vinegar stir-fried E.kansui group with 8 rats in each group.The blank group was given 0.5%carboxymethylcellulose sodium(CMC-Na)by gavage,and the E.kansui group and vinegar stir-fried E.kansui group were given the corresponding test solution for 20 days.The livers were collected on the 20th day.Rat liver samples were analyzed by ultra-high performance liquid chromatography-quadrupole-orbital trap high resolution mass spectrometry(UPLC-QExactive-MS).The data were processed by Compound Discoverer 3.0 software,and HMDB and other databases were searched.The differential metabolites were analyzed by principal component analysis(PCA),orthogonal partial least squares-discriminant analysis(OPLS-DA),and MetaboAnalyst to analyze the significant enrichment pathways of the obtained differential metabolites.RESULTS In the end,28 differential metabolites with biological significance were found between the E.kansui group and the blank group,18 metabolites were found with significant differences between the vinegar stir-fried E.kansui group and the blank group,and there were 13 metabolites in the intersection.CONCLUSION By increasing the levels of taurodeoxycholic acid and stearylcarnitine in liver,fermented vinegar can reduce the potential risk of early brain injury and type 2 diabetes.It can promote the regulation of immune function by increasing the level of glycocholic acid in liver.It can promote neurovascular remodeling and functional recovery after ischemic stroke by increasing the level of 20-hydroxyeicosaptaenoic acid in liver.By increasing the levels of 3-hydroxybutyric acid and oleo ethanolamine in liver,it shows anti-tumor,anti-oxidation and neuroprotection effects.The metabolic pathways involved in its attenuated mechanism are arachidonic acid
作者
杨晓旭
李文兰
YANG Xiaoxu;LI Wenlan(School of Pharmacy,Harbin University of Commerce,Heilongjiang Harbin 150001,China)
出处
《中国医院药学杂志》
CAS
北大核心
2024年第3期274-286,共13页
Chinese Journal of Hospital Pharmacy
基金
黑龙江省重点研发计划(编号:GZ20210092)
黑龙江省中医经典普及化专项课题(编号:ZYW2023-078)。
关键词
甘遂
炮制减毒
肝脏代谢组学
目标生物标志物
代谢通路
Euphorbia kansui
processing and detoxification
liver metabolomics
target biomarkers
metabolic pathways
