基于尿液代谢组学探讨白藜芦醇防治痛风性关节炎的作用机制

Mechanism of Resveratrol against Gouty Arthritis Based on Urine Metabolomics

目的:本研究旨在通过尿液代谢组学技术,揭示白藜芦醇在痛风性关节炎的潜在作用机制。方法:大鼠分为正常对照组、模型对照组、秋水仙碱阳性对照0.3 mg/kg组、白藜芦醇0.25、0.5、1 g/kg组。除正常对照组外,其余大鼠右下肢踝关节腔注射尿酸钠溶液25 mg/mL,正常对照组于同一部位关节腔注射生理盐水;各组灌胃给予相应药物,连续给药7 d;采用超高效液相色谱串联飞行时间质谱分析技术(UPLC-Q-TOF-MS)对正常对照组、模型对照组、白藜芦醇1 g/kg组大鼠尿液代谢组学进行分析,采用主成分分析法探寻潜在的关键性生物标志物,联合人类代谢组学数据库(HMDB)和京都基因与基因组百科全书数据库(KEGG)找出对应的相关代谢通路。结果:在痛风性关节炎模型大鼠尿液样本中发现17个潜在生物标志物,涉及12条相关代谢通路,其中,苯丙氨酸、酪氨酸和色氨酸的生物合成、牛磺酸和次牛磺酸代谢、嘌呤代谢为至关重要的代谢途径。结论:本研究通过尿液代谢组学技术,揭示了白藜芦醇抗痛风性关节炎的基本机制,为其今后的研究以及药物开发提供了有价值的参考。

Objective:To uncover the potential mechanism of resveratrol against gouty arthritis by urine metabolomics technique.Methods:Rats were divided into a normal control group,a model control group,a colchicine positive control group,and high-,medium-,and low-dose resveratrol groups(1,0.5,and 0.25 g/kg).Rats,except for those in the normal control group,were injected with 0.2 mL of sodium urate solution in the ankle joint,specifically,25 mg/mL into the ankle joint cavity of the right hind limb,while those in the normal control group were injected with physiological saline at the same joint site.Except for the normal control group and the model control group,the other groups were administered continuously for 7 days.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS)was used to analyze the urine metabolomics of rats in the normal control group,the model control group,and the high-dose resveratrol group.Principal component analysis(PCA)was used to explore potential key biomarkers.The Human Metabolome Database(HMDB)and the Kyoto Encyclopedia of Genes and Genomes(KEGG)were used to find corresponding related metabolic pathways.Results:Seventeen potential biomarkers were found in the urine samples of gouty arthritis model rats,involving 12 related metabolic pathways.Among them,the biosynthesis of phenylalanine,tyrosine,and tryptophan,as well as the metabolism of taurine and hypotaurine,and purine metabolism were identified as crucial metabolic pathways.Conclusion:This study,through urine metabolomics technology,reveals the basic mechanism of resveratrol against gouty arthritis,providing valuable references for future research and drug development in this area.