主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

北京中医药大学学报 ›› 2019, Vol. 42 ›› Issue (12): 1016-1023.doi: 10.3969/j.issn.1006-2157.2019.12.008

• 中药药理 • 上一篇    下一篇

基于1H-NMR的中西药干预 Wilson 病铜负荷大鼠肝损伤代谢组学研究*

张娟1, 谢道俊1, 鲍远程1, 许晶晶2, 沈桂平2#, 韩辉1, 董婷1, 黄晓峰1   

  1. 1 安徽中医药大学第一附属医院 安徽 230031;
    2 厦门大学电子科学与技术学院
  • 收稿日期:2019-06-30 出版日期:2019-12-30 发布日期:2020-01-06
  • 通讯作者: 沈桂平,男,博士,副教授,硕士生导师,主要研究方向:核磁共振方向研究,E-mail:gpshen@xmu.edu.cn
  • 作者简介:张娟,女,博士,副主任医师,副教授,硕士生导师
  • 基金资助:
    *国家自然科学基金面上项目(No.81774299),安徽省自然科学基金面上项目(No.170805MH199)

1H-NMR-based metabolomics investigation into intervention with Chinese herbs and conventional pharmaceuticals of copper-overload-induced liver injury in rats with Wilson’s disease*

Zhang Juan1, Xie Daojun1, Bao Yuancheng1, Xu Jingjing2, Shen Guiping2#, Han Hui1, Dong Ting1, Huang Xiaofeng1   

  1. 1 Department of Neurology,The First Affiliated Hospital of Anhui University of Chinese Medicine, Anhui 230031, China;
    2 School of Electronic Science and Engineering,Xiamen University,Fujian 361005,China
  • Received:2019-06-30 Online:2019-12-30 Published:2020-01-06
  • Contact: Associate Prof.Shen Guiping, Ph.D., Master’s Supervisor.Xiamen University.No. 422, Siming South Road, Siming District, Xiamen 361005.E-mail: gpshen@xmu.edu.cn

摘要: 目的 从代谢组学角度探讨中西药对Wilson病(WD)铜负荷大鼠模型肝损伤代谢网络的干预机制。方法 105只大鼠按照随机数字表分为7组,每组15只,分别为对照组、模型组、肝豆灵组、青霉胺组、谷胱甘肽组、SB203580组、SB203580肝豆灵组,按照文献方法复制Wilson病铜负荷大鼠模型,共计12周。从第7周开始,各干预组予以等效剂量相应药物,对照组和模型组予以等容量生理盐水灌胃,直至模型复制结束。采用 1H-NMR 代谢组学技术结合多元统计方法,阐述Wilson病肝损伤的肝脏代谢轮廓变化及分析不同治法对其生物标志物的干预作用。结果 WD铜负荷大鼠模型肝脏发生明显纤维化改变,不同方法干预后肝纤维化可不同程度减轻。WD铜负荷大鼠模型肝脏酮体代谢含量升高,肌酸含量下降;青霉胺干预后,谷胱甘肽、天冬氨酸盐、肌酸、氨基酸、缬氨酸、酪氨酸、组氨酸、嘧啶、嘌呤含量上升;SB203580肝豆灵组,肌酸上升,甲胺下降;谷胱甘肽及SB203580组,谷胱甘肽、缬氨酸、组氨酸、嘧啶、嘌呤含量上升。结论 中西医不同干预方法影响WD铜负荷大鼠肝脏组织谷胱甘肽、肌酸、酮体、氨基酸、嘧啶、嘌呤代谢,并有调节以上小分子物质代谢紊乱的作用,进而对WD铜负荷大鼠肝损伤有一定的修复作用。

关键词: 肝豆状核变性, 肝损伤, 中西药, 代谢组学, 大鼠

Abstract: Objective To explore the intervention mechanism of Chinese medicinal herbs and conventional pharmaceuticals on copper-overload-induced liver injury in rats with Wilson’s disease(WD). Methods 105 Wistar rats were randomly divided into 7 groups (15 in each group), including control group, model group,Gandouling(GDL)group, penicillamine group, glutathione group, model+SB203580 group,and GDL+SB203580 group.Rat models with copper overload were firstly established in 12 weeks according to relevant literature.Since the 7th week, all intervention groups were given intragastrically corresponding medicinals respectively in equivalent dose. Meanwhile, the control group and the model group were given the same volume of saline intragastrically until the models were established.Then 1HNMR metabonomics technology was used in combination with multivariate statistic analysis to elucidate the changes in liver metabolic profile caused by liver injury in rats with WD and to analyze the intervention effects of different treatments on its biomarkers. Results Obvious fibrosis was detected in copper-laden rats with WD, and liver fibrosis could be alleviated in different degrees with intervention in all treatment groups. There were an increase in metabolic content of ketones and a decrease in creatine content in the liver of the rat models.After intervention with penicillamine,there were increases in contents of glutathion, aspartic acid, creatine, amino acid, valine, tyrosine, histidine,pyrimidine and purine;with GDL and SB203580, increases in creatine and decreases in methylamine; and with glutathione and SB203580,increases in the contents of glutathione,valine, histidine, pyrimidine and purine. Conclusion Different interventions with Chinese medicinal herbs and conventional pharmaceuticals regulated metabolic disorders of such small molecules as glutathion, creatine, ketosome, amino acid, pyrimidine and purine in liver tissue of copper-laden rats with WD and hence can repair to some extent the copper-overload-induced liver injury in rats with WD.

Key words: hepatolenticular degeneration, liver injury, Chinese medicinal herbs and conventional pharmaceuticals, metabonomics, rats

中图分类号: 

  • R285.5