基于代谢组学和网络药理学的复方黑骨藤有效组分抗类风湿性关节炎机制研究  

Mechanism of active ingredients in Periploca forrestii compound against rheumatoid arthritis based on integrative metabolomics and network pharmacology

作　　者：张琴 张宏[1,2] 杨春梅[3] 王博 李晨阳 李琪 ZHANG Qin;ZHANG Hong;YANG Chun-mei;WANG Bo;LI Chen-yang;LI Qi(College of Life Sciences,Sichuan Normal University,Chengdu 610101,China;Plant Functional Genome and Bioinformatics Research Center,Sichuan Normal University,Chengdu 610101,China;Chengdu Product Quality Supervision and Inspection Institute,Chengdu 610101,China)

机构地区：[1]四川师范大学生命科学学院,四川成都610101 [2]四川师范大学植物功能基因组及生物信息研究中心,四川成都610101 [3]成都市产品质量监督检验研究院,四川成都610101

出　　处：《中国中药杂志》2023年第2期507-516,共10页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(31240087);九寨沟地震灾区珍稀动物受损栖息地林草植被快速恢复模式研究与示范项目(HX20200475);四川师范大学实验室创新研究项目(SYJS2021015)。

摘　　要：该实验利用超高效液相色谱-四极杆-飞行时间高分辨率质谱(ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer,UPLC-Q-TOF-HRMS)技术探讨复方黑骨藤有效组分对胶原诱导性关节炎(collagin-induced arthritis,CIA)大鼠脾脏代谢组的影响,并通过网络药理学分析其潜在抗炎机制。造模成功后,给药28 d,取大鼠脾脏组织,处理后采集UPLC-Q-TOF-HRMS谱,利用主成分分析(principal component analysis,PCA)、正交偏最小二乘法判别分析(orthogonal partial least squares discriminant analysis,OPLS-DA)以及MetPA方法对其进行分析。结果表明与空白对照组相比,模型组中肌苷、胞内胆碱、次黄嘌呤、牛磺酸等22种生物标志物含量显著升高,而CDP-乙醇胺、磷酰胆碱等9种生物标志物含量显著降低;与模型组相比,复方黑骨藤有效组分可使肌苷、胞内胆碱、CDP-乙醇胺、磷酰胆碱等21种生物标志物明显回调;差异代谢物通路富集分析显示共涉及17条通路,主要包括嘌呤代谢、牛磺酸与亚牛磺酸代谢、甘油磷脂代谢以及半胱氨酸与甲硫氨酸代谢。此外,网络药理学分析发现嘌呤代谢、甘油磷脂代谢、半胱氨酸与甲硫氨酸代谢等在类风湿性关节炎病理过程中占重要地位。该研究表明复方黑骨藤有效组分可通过改善CIA大鼠的脾脏代谢紊乱来延缓机体炎症反应的发生发展,揭示复方黑骨藤有效组分具有多靶点、多途径的抗炎机制,为复方黑骨藤有效组分抗类风湿性关节炎作用机制做出了新的解释。In this study,an ultra-performance liquid chromatography-quadrupole time-of-flight high resolution mass spectrometer(UPLC-Q-TOF-HRMS)was used to investigate the effects of the active ingredients in Periploca forrestii compound on spleen metabolism in rats with collagen-induced arthritis(CIA),and its potential anti-inflammatory mechanism was analyzed by network pharmacology.After the model of CIA was successfully established,the spleen tissues of rats were taken 28 days after administration.UPLC-Q-TOF-HRMS chromatograms were collected and analyzed by principal component analysis(PCA),orthogonal partial least squares discriminant analysis(OPLS-DA),and MetPA.The results showed that as compared with the blank control group,22 biomarkers in the spleen tissues such as inosine,citicoline,hypoxanthine,and taurine in the model group increased,while 9 biomarkers such as CDP-ethanolamine and phosphorylcholine decreased.As compared with the model group,21 biomarkers such as inosine,citicoline,CDP-ethanolamine,and phosphorylcholine were reregulated by the active ingredients in P.forrestii.Seventeen metabolic pathways were significantly enriched,including purine metabolism,taurine and hypotaurine metabolism,glycerophospholipid metabolism,and cysteine and methionine metabolism.Network pharmacology analysis found that purine metabolism,glycerophospholipid metabolism,and cysteine and methionine metabolism played important roles in the pathological process of rheumatoid arthritis.This study suggests that active ingredients in P.forrestii compound can delay the occurrence and development of inflammatory reaction by improving the spleen metabolic disorder of rats with CIA.The P.forrestii compound has multi-target and multi-pathway anti-inflammatory mechanism.This study is expected to provide a new explanation for the mechanism of active ingredients in P.forrestii compound against rheumatoid arthritis.

关 键 词：脾脏代谢组学 复方黑骨藤 有效组分 类风湿性关节炎 网络药理学 UPLC-Q-TOF-HRMS 

分 类 号：R285.5[医药卫生—中药学]