College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, P.R. China.
Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Zhanjiang 524088, P.R. China.
Food Funct. 2022 Sep 22;13(18):9434-9442. doi: 10.1039/d2fo01533a.
This study aims to investigate the anti-hyperuricemia effect and mechanism of anserine in hyperuricemic rats. Hyperuricemic rats were induced with a combination of 750 mg per kg bw d potassium oxazinate (PO) and 200 mg per kg bw d hypoxanthine for a week, and the rats were separately orally administered anserine (20, 40, 80 mg kg) and allopurinol (10 mg kg) for three weeks. The results show that the content of serum uric acid (SUA) decreased by approximately 40% and 60% after the intervention of anserine and allopurinol, respectively. The activity of superoxide dismutase (SOD) was increased and the levels of malondialdehyde (MDA), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were significantly decreased in the anserine groups. After the administration of anserine, the contents of blood urea nitrogen (BUN) and creatinine (Cr) were reduced in the kidney, and the levels of the proinflammatory cytokines IL-1β, IL-6β, TNF-α and TGF-β and inflammatory cell infiltration were reduced in both the liver and kidney. Moreover, the gene expressions of xanthine oxidase (XOD), renal urate transporter 1 (URAT1) and glucose transporter type 9 (GLUT9) were downregulated by anserine administration, and the gene expressions of ATP-binding cassette transporter G2 (ABCG2), organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) were upregulated at the same time. These findings suggest that hepatorenal injury was repaired by anserine, which further regulated the expression of hepatic XOD and renal URAT1, GLUT9, ABCG2, OAT1 and OAT3 to relieve hyperuricemia in rats.
本研究旨在探讨鹅肌肽对高尿酸血症大鼠的抗高尿酸血症作用及其机制。高尿酸血症大鼠采用 750mg/kg bw d 氧嗪酸钾（PO）和 200mg/kg bw d 次黄嘌呤联合腹腔注射诱导，连续 7 天，随后分别灌胃给予鹅肌肽（20、40、80mg/kg）和别嘌醇（10mg/kg）3 周。结果表明，鹅肌肽和别嘌醇干预后，血清尿酸（SUA）含量分别降低了约 40%和 60%。鹅肌肽组超氧化物歧化酶（SOD）活性升高，丙二醛（MDA）、碱性磷酸酶（ALP）和丙氨酸氨基转移酶（ALT）水平显著降低。鹅肌肽给药后，大鼠肾脏的血尿素氮（BUN）和肌酐（Cr）含量降低，肝脏和肾脏的促炎细胞因子白细胞介素-1β（IL-1β）、白细胞介素-6β（IL-6β）、肿瘤坏死因子-α（TNF-α）和转化生长因子-β（TGF-β）水平以及炎性细胞浸润减少。此外，鹅肌肽给药下调了黄嘌呤氧化酶（XOD）、肾脏尿酸盐转运蛋白 1（URAT1）和葡萄糖转运蛋白 9（GLUT9）的基因表达，同时上调了三磷酸腺苷结合盒转运蛋白 G2（ABCG2）、有机阴离子转运蛋白 1（OAT1）和有机阴离子转运蛋白 3（OAT3）的基因表达。这些发现表明，鹅肌肽修复了肝肾功能损伤，进一步调节了肝脏 XOD 和肾脏 URAT1、GLUT9、ABCG2、OAT1 和 OAT3 的表达，缓解了大鼠的高尿酸血症。
