微透析结合代谢组学探究佐剂性关节炎大鼠的代谢扰动及牛膝总皂苷的干预作用  

Microdialysis combined with metabonomics in exploring metabolic disturbance ofadjuvant arthritis rats and intervention effect of Achyranthes bidentata saponins

作　　者：张衡 吴虹[1,2] 卜妍红 孙明慧 邓然 王言 王梦蝶 王荣慧 吴欢 ZHANG Heng;WU Hong;BU Yan-hong;SUN Ming-hui;DENG Ran;WANG Yan;WANG Meng-die;WANG Rong-hui;WU Huan(College of Pharmacy,Anhui University of Chinese Medicine,Hefei 230012,China;Key Laboratory of Xin’an Medicine,Ministry of Education,Anhui Province Key Laboratory of Research&Development of Chinese Medicine,Anhui Province Key Laboratory of Chinese Medicinal Formula,Hefei 230012,China)

机构地区：[1]安徽中医药大学药学院,安徽合肥230012 [2]新安医学教育部重点实验室,中药研究与开发安徽省重点实验室,中药复方安徽省重点实验室,安徽合肥230012

出　　处：《中国药理学通报》2021年第6期877-884,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金面上项目(No 81473400);安徽中医药大学校级探索项目(No 2017HXTS37)。

摘　　要：目的使用微透析采样技术结合超高效液相色谱串联四极杆飞行时间质谱(UPLC-Q-TOF/MS)技术探究牛膝总皂苷(achyranthes bidentate saponins,ABS)干预类风湿关节炎(rheumatoid arthritis,RA)的代谢相关机制。方法将SD大鼠随机分为佐剂性关节炎(adjuvant induced arthritis,AA)模型组、空白对照组和ABS给药组,采用弗氏完全佐剂诱导AA大鼠模型,利用大鼠关节肿胀度、关节炎评分及滑膜组织病理学评价ABS对AA的干预效果;利用UPLC-Q-TOF/MS采集各组大鼠的关节腔微透析液样品信息。结果ABS给药后d6对AA大鼠的足爪肿胀具有抑制作用且能改善关节炎评分(P<0.05),并能改善大鼠滑膜组织病理形态;在关节腔微透析液中共筛选出19个与ABS干预AA相关的潜在生物标志物,通过通路富集分析发现它们主要涉及嘌呤代谢、嘧啶代谢、脂肪酸合成及类固醇激素合成途径。结论微透析结合代谢组学能够揭示ABS干预RA的代谢相关机制,为ABS作用机制的深入探讨奠定基础。Aim To use microdialysis technology combined with ultra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)technology to study the effect of Achyranthes bidentata saponins(ABS)on rheumatoid arthritis(RA)and its mechanisms.Methods SD rats were randomly divided into adjuvant arthritis(AA)model group,blank control group and ABS administration group.AA rat model was induced by Freund’s complete adjuvant.UPLC-Q-TOF/MS was used to collect joint cavity microdialysis fluid sample information of each group of rats.Results On 6th day after administration of ABS,an inhibitory effect on the paw swelling,improved the arthritis score(P<0.05),and better the pathological morphology of the synovial tissues were found in AA rats.Nineteen potential biomarkers were discovered and identified.Pathway enrichment analysis revealed that they mainly involved purine metabolism,pyrimidine metabolism,fatty acid biosynthesis and steroid hormone biosynthesis pathway.Conclusions Microdialysis combined with metabolomics can reveal the metabolic mechanism of ABS intervention on RA,laying a foundation for further study of the mechanism of ABS.

关 键 词：牛膝总皂苷 类风湿关节炎 代谢组学 UPLC-Q-TOF/MS 微透析 生物标志物 

分 类 号：R-332[医药卫生] R284.1