摘要
目的基于代谢组学和蛋白质组学探讨防己治疗痛风性关节炎的作用机制。方法运用尿酸钠诱导痛风性关节炎模型。随后,关节滑膜组织样本被用于组织病理学、代谢组学和蛋白质组学分析。最后,运用酶联免疫吸附测定法验证组学的分析结果。结果防己减轻了由尿酸钠诱导的滑膜组织的损伤,并逆转了30个代谢物和53个蛋白质的异常表达,这些靶点参与了10个病理学过程(例如炎症、凋亡及软骨损伤等)。通过联合通路分析,其中的4个代谢物和3个蛋白质共同参与了2个关键性通路(不饱和脂肪酸的生物合成和白细胞跨内皮迁移)。在验证性实验中,防己可以逆转大鼠滑膜中由尿酸钠诱导的花生四烯酸、前列腺素E2、钙粘着蛋白5及非受体型酪氨酸蛋白磷酸酶11的异常表达。结论本研究为防己在治疗痛风性关节炎上的应用提供了科学依据。
Objective To investigate the mechanism of Stephania tetrandra S.Moore(ST)in the treatment of gouty arthritis(GA)based on metabonomics and proteomics.Methods The GA model was induced by monosodium urate.Subsequently,synovial tissue samples from the joints were obtained for histopathological,metabonomics and proteomics analyses.Finally,enzyme-linked immunosorbent assay was used to validate the omics findings.Results ST attenuated synovial damage and showed the tendency to correct the dysregulation of 30 Metabolites and 53 proteins in GA rat model,which was involved in ten pathological processes(e.g.inflammation,apoptosis,and cartilage damage,etc.).Through the joint pathway analysis,4/30 metabolites and 3/53 proteins were involved in 2 key pathways(Biosynthesis of unsaturated fatty acids and Leukocyte transendothelial migration).In the verification experiment,ST could reverse the abnormal expressions of arachidonic acid,prostaglandin E2,cadherin 5,and tyrosine-protein phosphatase non-receptor type 11 induced by monosodium urate in rat synovial membrane.Conclusion The current study provides the scientific evidence for the application of ST in prescriptions for treating GA.
作者
张帅男
李红美
李煦照
ZHANG Shuainan;LI Hongmei;LI Xuzhao(College of Pharmacy,Guizhou University of Traditional Chinese Medicine,Guian New Area 550025,China)
出处
《沈阳药科大学学报》
CAS
CSCD
北大核心
2023年第7期941-947,共7页
Journal of Shenyang Pharmaceutical University
基金
贵州省科技计划项目(黔科合基础[2019]1037号)。
关键词
痛风性关节炎
防己
代谢组学
蛋白质组学
gouty arthritis
Stephania tetrandra S.Moore
metabonomics
proteomics
