摘要
目的:基于代谢组学技术探讨来氟米特干预类风湿关节炎(RA)大鼠的作用机制。方法:使用CⅡ型胶原诱导雌性Wistar大鼠建立稳定的RA模型。来氟米特治疗21天后,评价各组大鼠关节肿胀情况,分析踝关节切片病理染色结果,检测血清IL-1β、IL-6和IgG含量并计算脾指数。利用代谢组学技术研究疾病导致的体内代谢变化,并分析药物干预疾病的代谢通路。结果与结论:来氟米特可显著改善RA大鼠关节肿胀度及踝关节病理变化,并降低大鼠血清中的IL-1β、IL-6和IgG水平(P<0.01)。血清代谢组学结果表明,来氟米特通过显著回调14个内源化合物,干预谷胱甘肽、半胱氨酸、蛋氨酸、花生四烯酸、色氨酸及嘌呤的代谢,发挥对RA大鼠的保护作用。
Objective:To investigate the intervention mechanism of leflunomide in rats with rheumatoid arthritis(RA)based on metabolomics.Methods:We established a stable RA model by CⅡtype collagens.After 21 days of drug treatment,the swelling of rats in each group was evaluated.Pathological staining was performed on the ankle sections of rats in each group,and the serum contents of IL-1β,IL-6 and IgG and spleen indexes were evaluated.Metabolomics technology was used to analyze the metabolic changes caused by RA,and the metabolic pathways of drug intervention.Results&Conclusion:Leflunomide significantly decreased the swelling degrees,ankle joint pathological changes and serum levels of IL-1β,IL-6 and IgG(P<0.01).Metabolomics study revealed that leflunomide played a protective effect on RA rats by significantly reversing the contents of 14 endogenous compounds and intervened the metabolism of glutathione,cysteine,methionine,arachidonic acid,tryptophan and purine.
作者
张欣亚
王碧莹
贾福康
付钰
ZHANG Xinya;WANG Biying;JIA Fukang;FU Yu(School of Pharmacy,Henan University of Chinese Medicine,Zhengzhou 450046,China;Henan Lingrui Pharmaceutical Company,Xinyang,He'nan 464000,China)
出处
《药学与临床研究》
2023年第3期193-200,共8页
Pharmaceutical and Clinical Research
基金
国家自然科学基金(81703680)。
