降血尿酸益生菌株的筛选和降血尿酸机理的探索

Isolation of hypouricemic probiotics and exploration their effects on hyperuricemic rats

摘要:

【背景】高尿酸血症是人体内血尿酸含量显著高于正常水平的代谢性疾病，利用益生菌降解食物中外源性嘌呤类成分成为治疗高尿酸血症的新方法。【目的】筛选具有降低血尿酸作用的益生菌，并探索其作用机制。【方法】利用HPLC从多株实验菌株中筛选降解核苷酸(腺苷酸、鸟苷酸)、核苷(腺苷、鸟苷)、嘌呤(黄嘌呤、次黄嘌呤、鸟嘌呤)、尿酸能力最强的益生菌。首次利用质谱定性与定量检测菌株降解核苷与核苷酸过程中代谢物的变化，结合菌株对高尿酸血症模型大鼠血尿酸水平的影响，初步探索其降低血尿酸的机理。【结果】首次筛选出具有较强降解核苷酸与核苷能力的干酪乳杆菌ZM15 (CGMCC No.13980)，高尿酸血症模型大鼠验证其具有降低血尿酸的作用。结果显示菌株ZM15在胞内降解核苷酸、核苷后，胞内、外均测到鸟嘌呤、黄嘌呤、次黄嘌呤，且胞内3种嘌呤含量显著高于正常菌体内含量(P<0.01)，尿酸和尿囊素在胞内、外均未发现。【结论】干酪乳杆菌ZM15具有较强的降解核苷酸、核苷的能力，推测其主要通过与肠道上皮细胞竞争吸收核苷酸与核苷，从而对高尿酸血症模型大鼠具有降血尿酸作用。

Abstract:

[Background] Hyperuricemia is well-known as a kind of metabolic disease with abnormal higher serum uric acid level. It is becoming a new method for treating hyperuricemia by degrading exogenous purine components ingested from food through probiotics. [Objective] Thirty probiotic strains of thirteen species were investigated for their abilities of lowering serum uric acid, we preliminarily propose the mechanism of its effects on hyperuricemic rats. [Methods] The ability of degrading nucleotides (adenosine monophosphate, guanosine monophosphate) , nucleosides (adenosine, guanosine), purines (xanthine, hypoxanthine and guanine) and uric acid by different probiotics were determined with HPLC, the probiotic strain with the fastest degrading ability was selected as the candidate strain for further test on hyperuricemic rats. Metabolites in the process of degrading nucleosides and nucleotides by probiotics were detected by mass, the mechanism of probiotics lowering the blood uric acid was preliminarily explored. [Results] Lactobacillus casei ZM15 was selected with the highest degradation rates of nucleosides and nucleotides. The animal experimental results showed that ZM15 had effects on hyperuricemia. Mass spectrometry results showed that after degradation of nucleotides and nucleotides in cell, guanine, xanthine and hypoxanthine appeared both inside and outside ZM15 cells, three kinds of purine content were markedly higher than those in normal cells, uric acid and allantoin were not found both inside and outside. [Conclusion] Lactobacillus casei ZM15 has the fasted degradation ability of nucleotide and nucleotide, and it has obvious effects of lowering uric acid on hyperuricemic model rats by mechanism of competition.