世界中医药

目的:采用代谢组学技术探究甲氨蝶呤抗类风湿性关节炎的作用机制。方法:采用佐剂性关节炎（AIA）方法复制大鼠类风湿性关节炎模型，采用经典足肿胀度指标评价模型复制程度，并给予甲氨蝶呤进行治疗。收集血液样本采用代谢轮廓技术表征疾病发生发展及给予药物干预后的代谢水平，采用MSE数据采集模式全成分获取各组大鼠的实验过程中的生物学信息，并通过模式识别、富集分析等手段以整体分析到局部的聚焦分析方法获取与类风湿性关节炎相关的核心代谢酶及血液生物标记物。进而阐明类风湿性关节炎的发病机制及甲氨蝶呤的作用机制。结果:非靶向代谢轮廓分析显示，甲氨蝶呤对类风湿性关节炎大鼠的整体代谢由明显的干预作用，代谢轮廓由模型状态向空白组状态发生偏移，从整体代谢角度证明甲氨蝶呤对类风湿性关节炎鼠有良好的疗效。通过正交偏最小二乘判别分析中的S图聚焦获取类风湿性关节炎大鼠血液相关代谢异常标记物，如鸟苷五磷酸腺苷、葡萄醛酸胆红素、鸟苷二磷酸、硬脂酸等。通路分析显示来发现类风湿性关节炎大鼠主要涉及脂肪酸生物合成、淀粉和蔗糖代谢、嘧啶代谢、戊糖和葡萄糖醛酸化、嘌呤代谢。结论:甲氨蝶呤对类风湿性关节炎大鼠有良好的治疗作用。通过整体的对脂肪酸生物合成等代谢通路中关键代谢酶及代谢标记物的调节作用可能起到抑制类风湿性关节炎的作用。

English Summary:

To explore the anti-rheumatoid arthritis mechanism of methotrexate by using metabonomic techniques.Methods:The model of rheumatoid arthritis in rats was replicated by adjuvant arthritis (AIA).The replication degree of the model was evaluated by classical foot swelling index and treated with methotrexate.Serum samples were collected to characterize the occurrence and development of diseases and the metabolic level after drug intervention by metabolic profiling technology.Biological information of each group of rats was obtained by MSE data acquisition mode during the experiment.Core metabolic enzymes related to rheumatoid arthritis were obtained by pattern recognition，enrichment analysis and other methods.The pathogenesis of rheumatoid arthritis and the action mechanism of methotrexate were further elucidated.Results:Non-targeted metabolic profile analysis showed that methotrexate had an obvious intervention effect on the overall metabolism of rheumatoid arthritis rats，and the metabolic profiles shifted from model state to blank group state.It was proved that methotrexate had a good effect on rheumatoid arthritis rats from the point of view of overall metabolism.The blood-related metabolic abnormality markers such as guanosine Pentaphosphate adenosine，glucuronic acid bilirubin，guanosine diphosphate，stearic acid，in rheumatoid arthritis rats were obtained by S-map focusing in orthogonal partial least squares discriminant analysis.Pathway analysis showed that fatty acid biosynthesis，starch and sucrose metabolism，pyrimidine metabolism，pentose and glucuronidation，purine metabolism were mainly involved in rheumatoid arthritis rats.Conclusion:Methotrexate has a good therapeutic effect on rheumatoid arthritis rats.The regulation of key metabolic enzymes and metabolic markers in metabolic pathways such as fatty acid biosynthesis，starch and sucrose metabolism，pyrimidine metabolism may play a role in inhibiting rheumatoid arthritis.

查看全文查看/发表评论下载PDF阅读器