摘要
目的研究低极性人参皂苷对类风湿关节炎大鼠模型的干预效果,明确低极性人参皂苷发挥抗炎作用的代谢途径。方法将大鼠随机分成正常组、模型组、MTX组和低极性皂苷高、中、低剂量组,经口灌胃30d后低极性人参皂苷显著降低了RA大鼠模型的疾病程度,并通过超高效液相串联质谱(UPLC-MS)测定血清和滑膜组织代谢组学来探究低极性人参皂苷的干预机制。所得数据进行主成分分析和正交偏最小二乘法判别分析(OPLS-DA)。结果低极性人参皂苷高剂量组ESR与RF均显著下降(P<0.01)。代谢组学显示血清OPLS-DA中R2X为0.626,R2Y为0.904;滑膜组织OPLS-DA中R2X为0.429,R2Y为0.689,在模型组大鼠体内鉴定出主要差异代谢物包括花生四烯酸、缬氨酸、亚油酸、鸟嘌呤核苷等。在低极性皂苷高剂量组大鼠体内鉴定出主要差异代谢物包括亚油酸、甜菜碱、二十碳五烯酸、丙氨酸、甲硫氨酸亚砜、异亮氨酸等。结论代谢谱显示炎症与亚油酸代谢、缬氨酸,亮氨酸和异亮氨酸降解、花生四烯酸代谢等代谢途径相关,低极性皂苷调节了α-亚麻酸代谢、蛋氨酸代谢、葡萄糖丙氨酸循环等抗炎代谢途径。
Objective The therapeutic effect of less polar ginsenosides on rats with rheumatoid arthritis was studied,and the metabolic pathway that produce anti-inflammatory effect of less polar ginsenosides was identified.Methods Rats were randomly divided into the control group,the model group,methotrexate treatment group,and high dose,medium dose,and low dose less polar ginsenosides groups.After 30 days of oral administration,less polar ginsenosides reduced the disease activity significantly in rats with rheumatoid arthritis.Blood and ankle synovial tissue metabolisms were measured by ultra performance liquid chromatography(UPLC)tandem mass spectrometry(MS)to explore the mechanism of less polar ginsenosides.The resulting data were subjected to principal component analysis and orthogonal partial least squares discriminant analysis(OPLS-DA).Results Compared with the model group,erythrocyte sedimentation rate and RF decreased significantly in the high dose of less polar ginsenosides(P<0.01).Metabolomics showed that R2X and R2Y of serum OPLS-DA were 0.626 and 0.904 respectively.The R2X and R2Y of synovial OPLS-DA were 0.429 and 0.689 respectively.Major differential metabolites were identified in the model group of rats,including arachidonic acid,valine,linoleic acid,and guanine nucleoside,etc.The main differential metabolites were identified in rats in the high dose group of less polar ginsenosides,including linoleic acid,betaine,eicosapentaenoic acid,alanine,methionine sulfoxide,isoleucine,etc.Conclusion The metabolic spectrum has shown that inflammation is associated with linoleic acid metabolism,valine,leucine and isoleucine degradation,arachidonic acid metabolism.Less polar ginsenosides regulatethe linolenic acid metabolism,methionine metabolism and glucose alanine cycle.
作者
冯静
余远
宋林梦
高汉义
曹雨晴
陶飞燕
薛鹏
唐少坚
Feng Jing;Yu Yuan;Song Linmeng;Gao Hanyi;Cao Yuqing;Tao Feiyan;Xue Peng;Tang Shaojian(School of Rehabilitation,Weifang Medical University,Weifang 261053,China;School of Public Health,Weifang Medical University,Weifang 261053,China;Department of Rehabilitation Medicine,Affiliated Hospital of Weifang Medical University,Weifang 261053,China;School of Pharmacy,Weifang Medical University.Weifang 261053,China)
出处
《中华风湿病学杂志》
CAS
CSCD
北大核心
2023年第5期315-320,I0004,I0005,共8页
Chinese Journal of Rheumatology
基金
国家自然科学基金(32102106)
泰山学者工程专项经费(tsqn202211232)。
关键词
关节炎
类风湿
关节炎
实验性
大鼠
皂苷类
代谢组学
炎症
Arthritis,rheumatol
Arthritis,experimental,rate
Ginsenosides
Metabolomics
Inflammatinn
