Allopurinol, rutin, and quercetin attenuate hyperuricemia and renal dysfunction in rats induced by fructose intake: renal organic ion transporter involvement
Allopurinol, rutin, and quercetin attenuate hyperuricemia and renal dysfunction in rats induced by fructose intake: renal organic ion transporter involvement
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别嘌呤醇、芦丁和槲皮素减轻果糖摄入引起的大鼠高尿酸血症和肾功能障碍：肾脏有机离子转运蛋白参与
DOI：
10.1152/ajprenal.90767.2008
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发表时间：
2009-10-01
影响因子：
4.2
通讯作者：
Kong, Ling-Dong
中科院分区：
文献类型：
--
作者：
Hu, Qing-Hua;Wang, Chuang;Kong, Ling-Dong
胡强，王超，李军，张丁，孔林，别嘌呤醇，芦丁，和槲皮素减轻果糖摄入引起的大鼠高尿酸血症和肾功能障碍：肾脏有机离子转运体参与。Am J Physiol Renal Physiol 297：F1080-F1091,2009。2009年7月15日首次出版；DOI：10.1152/ajprenal.90767.2008。-果糖摄入最近与代谢综合征的流行有关，而高尿酸血症在果糖诱导的代谢综合征中起致病作用。果糖喂养的大鼠表现出高尿酸血症和肾功能障碍，尿酸/肌酐比值和尿酸排泄分数(FEUR)降低，以及代谢综合征的其他特征。用别嘌醇、芦丁和槲皮素降低血尿酸水平可增加尿酸/肌酐比值和FUR，并减轻果糖诱导的其他代谢异常，表明高尿酸血症是该模型肾脏尿酸排泄不足的原因之一。此外，我们还发现，果糖上调了大鼠肾脏rSLC2A9v2和肾脏特异性转运蛋白(RRST)的表达水平，下调了有机阴离子转运体(rOAT1和ruat)和有机阳离子转运体(rOCT1和rOCT2)的表达水平，同时上调了前列腺素E-2(PGE(2))的表达，降低了一氧化氮(NO)的表达。在果糖喂养的大鼠肾脏中，别嘌醇、芦丁和槲皮素通过PGE(2)降低和NO升高逆转了这些转运蛋白的失调。这些结果提示，肾脏rSLC2A9v2、rRST、rOAT1、RUAT、rOCT1和rOCT2的异常调节参与了果糖诱导的高尿酸血症和肾功能障碍。因此，这些肾脏转运体可能成为治疗果糖诱导代谢综合征中高尿酸血症和肾功能障碍的新靶点。
Hu Q, Wang C, Li J, Zhang D, Kong L. Allopurinol, rutin, and quercetin attenuate hyperuricemia and renal dysfunction in rats induced by fructose intake: renal organic ion transporter involvement. Am J Physiol Renal Physiol 297: F1080-F1091, 2009. First published July 15, 2009; doi:10.1152/ajprenal.90767.2008.-Fructose consumption has been recently related to an epidemic of metabolic syndrome, and hyperuricemia plays a pathogenic role in fructose-induced metabolic syndrome. Fructose-fed rats showed hyperuricemia and renal dysfunction with reductions of the urinary uric acid/creatinine ratio and fractional excretion of uric acid (FEur), as well as other features of metabolic syndrome. Lowering serum uric acid levels with allopurinol, rutin, and quercetin increased the urinary uric acid/creatinine ratio and FEur and attenuated other fructose-induced metabolic abnormalities in rats, demonstrating that hyperuricemia contributed to the deficiency of renal uric acid excretion in this model. Furthermore, we found that fructose upregulated the expression levels of rSLC2A9v2 and renal-specific transporter (rRST), downregulated the expression levels of organic anion transporters (rOAT1 and rUAT) and organic cation transporters (rOCT1 and rOCT2), with the regulators prostaglandin E-2 (PGE(2)) elevation and nitric oxide (NO) reduction in rat kidney. Allopurinol, rutin, and quercetin reversed dysregulations of these transporters with PGE(2) reduction and NO elevation in the kidney of fructose-fed rats. These results suggested that dysregulations of renal rSLC2A9v2, rRST, rOAT1, rUAT, rOCT1, and rOCT2 contributed to fructose-induced hyperuricemia and renal dysfunction. Therefore, these renal transporters may represent novel therapeutic targets for the treatment of hyperuricemia and renal dysfunction in fructose-induced metabolic syndrome.