基于UHPLC-HRMS血清代谢组学研究黄芪发酵菌质干预高尿酸血症的作用机制

Study on Mechanism of Fermentation of Astragalus Membranaceus on Serum Metabonomics in Hyperuricemia Based on UHPLC-HRMS

关键词:  黄芪发酵菌质  高尿酸血症  血清代谢组学  作用机制

Key words:  fermentation of Astragalus membranaceus  hyperuricemia  serum metabolomics  mechanism

摘要:

目的 基于UHPLC-HRMS血清代谢组学研究黄芪发酵菌质对高尿酸血症模型大鼠血清内源性代谢产物的影响及机制。方法 将SD大鼠随机分为空白组、模型组、苯溴马隆组(20 mg·kg^-1)和黄芪发酵菌质高剂量组(3.0 g·kg^-1)、低剂量组(1.5 g·kg^-1)。模型组和各给药组均先采用大鼠灌胃300 mg·kg^-1氧嗪酸钾建立高尿酸血症模型，造模后1 h给药组给予相应药物进行干预，14 d后采集大鼠血清。利用UHPLC-HRMS对不同组别大鼠血清中的内源性代谢产物进行分析，并结合多元数据统计分析方法筛选差异代谢物和代谢通路。结果 造模14 d后高尿酸血症大鼠模型建立成功，黄芪发酵菌质显示出良好的降尿酸作用。与空白组相比，模型组发现了17个与高尿酸血症发病相关的潜在生物标志物；黄芪发酵菌质可显著回调其中10个潜在生物标志物，并主要涉及鞘脂代谢、嘧啶代谢、色氨酸代谢、泛酸和辅酶A生物合成、甘氨酸、丝氨酸和苏氨酸代谢等通路发挥降尿酸作用。结论 本研究可为揭示黄芪发酵菌质降尿酸作用机制研究提供依据，并为黄芪的深度开发利用奠定基础。

Abstract:

OBJECTIVE To research the effect and mechanism of fermentation of Astragalus membranaceus on endogenous metabolites in hyperuricemia model rats using serum UHPLC-HRMS. METHODS The SD rats were randomly divided into different groups, including blank group, model group, benzbromarone group(20 mg·kg^-1), as well as fermentation of Astragalus membranaceus high-dose(3 g·kg^-1) and low-dose group(1.5 g·kg^-1). Model group and each treatment group were disposed with 300 mg·kg^-1 oxonic acid potassium to establish hyperuricemia models. At the time of 1 h after modeling, rats in each treatment group were given corresponding drugs for intervention. Collected rat serum after 14 d. The serum of different groups were collected for endogenous metabolites research using UHPLC-HRMS. After multivariate statistical analysis, the different metabolites and metabolic pathways were selected. RESULTS The hyperuricemia rat modes were successfully established by oxonic acid potassium 14 d, and fermentation of Astragalus membranaceus showed good uric acid reducing effect. Compared with the blank group, 17 potential biomarkers associated with hyperuricemia were found in the model group. Among them, 10 potential biomarkers were significantly recalled by fermentation of Astragalus membranaceus. It mainly involved sphingolipid metabolism, pyrimidine metabolism, tryptophan metabolism, pantothenic acid and CoA biosynthesis, glycine, serine and threonine metabolism and other pathway. CONCLUSION This study can provide a basis for revealing the mechanism of reducing uric acid by fermentation of Astragalus membranaceus, and lay a foundation for the further development and utilization of Astragalus.