大剂量龙胆泻肝汤治疗氧化性肝损伤引发肝毒性的代谢组学机制  

Metabolomic Mechanism of Hepatotoxicity Induced by Oxidative Liver Injury Treated with High-dose Longdan Xiegan Decoction

作　　者：张冉冉 张艳 杨秀东[1] ZHANG Ranran;ZHANG Yan;YANG Xiudong(School of Chemical and Pharmaceutical Engineering,Jilin Insititute of Chemical Technology,Jilin City 132022,China;School of Medicine,Jiaxing University,Jiaxing 314001,China)

机构地区：[1]吉林化工学院化学与制药工程学院,吉林吉林132022 [2]嘉兴大学医学院,浙江嘉兴314001

出　　处：《吉林化工学院学报》2024年第9期33-40,共8页Journal of Jilin Institute of Chemical Technology

摘　　要：采用D-半乳糖建立大鼠氧化性肝损伤模型,研究大剂量龙胆泻肝制剂治疗大鼠氧化性肝损伤时毒性作用产生的机制。连续给药60 d后处死大鼠,采集大鼠的肝脏及血液等生物样品。利用气质联用技术(GC-MS)对肝匀浆和血液中的相关标志物进行检测,利用代谢组学中经典的分析方法进行搜库,从而分析出在大剂量条件下的龙胆泻肝制剂对于治疗大鼠氧化性肝损伤过程中产生的差异代谢产物及其所反映出的毒性作用及其相关影响。通过对检测出的生物标志物进行代谢通路分析,最终确定影响大剂量龙胆泻肝制剂治疗大鼠氧化性肝损伤的毒性作用的产生机制。实验结果表明,大剂量龙胆泻肝制剂治疗时产生的毒性作用相关的生物标志物分别为2-氨基苯甲酸、柠檬酸、羟胺、酮戊二酸、胆固醇、肌氨酸、烟酸、烟酰胺、磷酸吡哆醛、衣康酸、磷酸甲酯、丙酮酸、酪氨酸、3-磷酸甘油醛、顺式乌头酸、草酰乙酸等16种代谢产物。龙胆泻肝的毒性作用机制可能与柠檬酸盐循环(TCA循环)、糖异生、苹果酸-天冬氨酸穿梭等3种代谢通路相关。D-galactose was used to establish a rat model of oxidative liver injury,and to study the mechanism of Longdan Xiegan Decoction(LXD)in the treatment of oxidative liver injury.Rats were killed after 30 days of continuous administration,and biological samples such as liver tissue and blood were collected as planned.Gas chromatography-mass spectrometry was used to detect the related markers in liver homogenate and blood,and metabonomic was used to search the database,to analyze the differential metabolites of LXD in the treatment of oxidative liver injury in rats,and to analyze the metabolic pathways of the detected markers,finally,the mechanism of LXD in the treatment of oxidative liver injury in rats was determined.The experimental results show that,the biomarkers associated with the treatment of oxidative liver injury in rats were citric acid,2-Aminobenzoic acid,hydroxylamine,α-ketoglutaric acid,cholesterol,sarcosine,nicotinic acid,nicotinamide,Pyridoxal Phosphate,itaconic acid,methyl phosphate,pyruvic acid,tyrosine,glyceraldehyde 3-phosphate,cisconite acid and oxalic acid.The mechanism of LXD may be related to three metabolic pathways:Gluconeogenesis,citrate cycle(TCA),acetyl entering Mitochondria,malate L-Aspartic acid shuttle and alanine metabolism.

关 键 词：毒性作用 龙胆泻肝制剂 GC-MS 代谢组学 氧化性肝损伤 

分 类 号：R575.5[医药卫生—消化系统]