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TSR332和TSF331可稳定大鼠血清尿酸水平并预防高尿酸血症。

TSR332 and TSF331 stabilize serum uric acid levels and prevent hyperuricemia in rats.

作者信息

Kuo Yi-Wei, Hsieh Shih-Hung, Chen Jui-Fen, Liu Cheng-Ruei, Chen Ching-Wei, Huang Yu-Fen, Ho Hsieh-Hsun

机构信息

Research and Development Department, Glac Biotech Co., Ltd., Tainan, Taiwan.

出版信息

PeerJ. 2021 May 3;9:e11209. doi: 10.7717/peerj.11209. eCollection 2021.

Abstract

BACKGROUND

Uric acid (UA) is the end product of purine metabolism in the liver and is excreted by the kidneys. When purine metabolism is impaired, the serum UA level will be elevated (hyperuricemia) and eventually lead to gout. During evolution, humans and some primates have lost the gene encoding uricase, which is vital in UA metabolism. With the advances of human society, the prevalence of hyperuricemia has dramatically increased because of the refined food culture. Hyperuricemia can be controlled by drugs, such as allopurinol and probenecid. However, these drugs have no preventive effect and are associated with unpleasant side effects. An increasing number of probiotic strains, which are able to regulate host metabolism and prevent chronic diseases without harmful side effects, have been characterized. The identification of probiotic strains, which are able to exert beneficial effects on UA metabolism, will provide an alternative healthcare strategy for patients with hyperuricemia, especially for those who are allergic to anti-hyperuricemia drugs.

METHODS

To elicit hyperuricemia, rats in the symptom control group (HP) were injected with potassium oxonate and fed a high-purine diet. Rats in the probiotic groups received the high-purine diet, oxonate injection, and supplements of probiotic strains TSR332, TSF331, or La322. Rats in the blank control group (C) received a standard diet (AIN-93G) and oxonate injection.

RESULTS

Purine-utilizing strains of probiotics were screened using high-pressure liquid chromatography (HPLC) in vitro, and the lowering effect on serum UA levels was analyzed in hyperuricemia rats in vivo. We found that strain TSR332 and strain TSF331 displayed significantly strong assimilation of inosine (90%; = 0.00003 and 59%; = 0.00545, respectively) and guanosine (78%; = 0.00012 and 51%; = 0.00062, respectively) within 30 min in vitro. Further animal studies revealed that serum UA levels were significantly reduced by 60% ( = 0.00169) and 30% ( = 0.00912), respectively, in hyperuricemic rats treated with TSR332 and TSF331 for 8 days. Remarkably, TSR332 ameliorated the occurrence of hyperuricemia, and no evident side effects were observed. Overall, our study indicates that TSR332 and TSF331 are potential functional probiotic strains for controlling the development of hyperuricemia.

摘要

背景

尿酸(UA)是肝脏中嘌呤代谢的终产物,由肾脏排泄。当嘌呤代谢受损时,血清尿酸水平会升高(高尿酸血症),最终导致痛风。在进化过程中,人类和一些灵长类动物失去了编码尿酸酶的基因,而尿酸酶在尿酸代谢中至关重要。随着人类社会的发展,由于精致的饮食文化,高尿酸血症的患病率急剧上升。高尿酸血症可以通过药物控制,如别嘌醇和丙磺舒。然而,这些药物没有预防作用,并且伴有令人不适的副作用。越来越多能够调节宿主代谢并预防慢性疾病且无有害副作用的益生菌菌株已被鉴定。鉴定出对尿酸代谢有有益作用的益生菌菌株,将为高尿酸血症患者,尤其是那些对抗高尿酸血症药物过敏的患者提供一种替代的医疗保健策略。

方法

为诱发高尿酸血症,症状对照组(HP)的大鼠注射氧嗪酸钾并喂食高嘌呤饮食。益生菌组的大鼠接受高嘌呤饮食、氧嗪酸钾注射,并补充益生菌菌株TSR332、TSF331或La322。空白对照组(C)的大鼠接受标准饮食(AIN - 93G)和氧嗪酸钾注射。

结果

使用高压液相色谱(HPLC)在体外筛选利用嘌呤的益生菌菌株,并在体内对高尿酸血症大鼠分析其对血清尿酸水平的降低作用。我们发现,菌株TSR332和菌株TSF331在体外30分钟内对肌苷(分别为90%;P = 0.00003和59%;P = 0.00545)和鸟苷(分别为78%;P = 0.00012和51%;P = 0.00062)表现出显著较强的同化作用。进一步的动物研究表明,用TSR332和TSF331治疗8天的高尿酸血症大鼠的血清尿酸水平分别显著降低了60%(P = 0.00169)和30%(P = 0.00912)。值得注意的是,TSR332改善了高尿酸血症的发生,且未观察到明显的副作用。总体而言,我们的研究表明TSR332和TSF331是控制高尿酸血症发展的潜在功能性益生菌菌株。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fb7/8101448/03b31b12dbdd/peerj-09-11209-g001.jpg

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