摘要
目的应用核磁共振氢谱(^(1)H-NMR)代谢组学技术分析苍耳子醇提物和水提物致小鼠肝脏中内源性代谢产物的变化,探索苍耳子致肝损伤的可能作用机制,寻找肝毒性的敏感标志物。方法将56只小鼠随机分为7组,分别为空白组(0.9%氯化钠溶液),苍耳子醇提物高、中、低剂量组(给药剂量分别为生药6、3、1.5 g/kg),苍耳子水提物高、中、低剂量组(给药剂量分别为生药6、3、1.5 g/kg),连续灌胃给药20 d,记录小鼠体质量,对肝脏和血清进行生化指标检测,并对肝脏组织进行病理形态学检查。运用^(1)H-NMR对肝脏样本进行分析,结合多变量统计分析筛选差异代谢物并进行代谢通路和疾病富集分析,利用Venn分析寻找给药组共同的差异代谢物,即潜在的肝毒性敏感标志物。结果除苍耳子醇提物低剂量给药组外其余各组均产生不同程度肝脏病变。代谢组学结果显示筛选出的差异代谢物主要被富集到氨基酸代谢、糖代谢、脂代谢等通路,共筛选出糖原(glycogen)、尿苷(uridine)、苯丙氨酸(phenylalanine)、马尿酸(hippurate)、乙酸(acetate)、丝氨酸(serine)6种敏感代谢标志物。结论苍耳子可能主要通过影响氨基酸、糖类、脂质等代谢对肝脏造成损伤,糖原、尿苷、苯丙氨酸、马尿酸、乙酸、丝氨酸可作为潜在的肝毒性敏感生物标志物。
Objective^(1)H-NMR metabolomics technology was used to analyze the changes of endogenous metabolites in the liver of mice induced by alcohol and water extracts of Cangerzi(Fructus Xanthii,FX),to explore the possible mechanism of action of FX on liver injury,and to search for sensitive markers of liver toxicity.Methods 56 mice were randomly divided into 7 groups:control group(normal saline),high,medium and low dose alcohol extract of FX(6,3 and 1.5 g/kg respectively),and high,medium and low dose water extract of FX(6,3 and 1.5 g/kg respectively).The mice were given medicine for 20 days,and their body weight was recorded.The biochemical indexes of liver and serum were detected,and the liver tissues were examined by pathomorphology.The liver samples were analyzed by nuclear magnetic resonance hydrogen spectroscopy(^(1)H-NMR),multivariate statistical analysis was used to identify the differential metabolites and to enrich thedisease and metabolicpathways involved in the differential metabolites.Venn analysis was used to find common differential metabolites in the administration group,namely potential sensitive markers of hepatotoxicity.Results Liver lesions of different degrees were observed in all groups except the low dose alcohol extract of FX.The metabonomics results showed that the screened differential metabolites were mainly enriched into amino acid metabolism,glucose metabolism,lipid metabolism and other pathways.Six biomarkers were identified,including glycogen,uridine,phenylalanine,hippurate,acetic and serine.Conclusion FX may damage the liver mainly by affecting the metabolism of amino acids,sugars and lipids,etc.Glycogen,uridine,phenylalanine,hippurate,acetic and serine can be used as potential biomarkers of liver toxicity sensitivity.
作者
王荣荣
吕佳霖
贺明帅
姜苗苗
WANG Rongrong;LYU Jialin;HE Mingshuai;JIANG Miaomiao(State Key Laboratory of Component-based Chinese Medicine,Tianjian University of Traditional Chinese Medicine,Tianjin 301617,China)
出处
《辽宁中医药大学学报》
CAS
2021年第10期34-39,共6页
Journal of Liaoning University of Traditional Chinese Medicine
基金
国家重点研发计划(2018YFC1707403)
天津市科技计划项目(20YJDJC00120)
关键词
苍耳子
肝毒性
核磁共振
代谢组学
敏感生物标志物
通路分析
Cangerzi(Fructus Xanthii)
hepatotoxicity
nuclear magnetic resonance
metabonomics
sensitive marker
pathway analysis
作者简介
王荣荣(1996-),女,山东德州人,硕士研究生,研究方向:药效物质基础研究;通讯作者:姜苗苗(1982-),女,辽宁沈阳人,研究员,博士,研究方向:中药药效物质基础。E-mail:miaomiaojiang@126.com。
