Nat Commun：研究揭示痛风其他病因

日本一个研究小组4月3日在英国《自然—通讯》杂志上在线发表研究论文称，他们发现痛风不光是肾脏排出尿酸的功能降低所致，肠道排出尿酸功能的降低也是一个致病原因。

痛风是由于嘌呤合成代谢增加、尿酸产生过多或因尿酸排泄不良而致血中尿酸升高，持续处于高尿酸血症的状态，痛风会引起剧烈的关节疼痛。迄今研究人员一直认为尿酸的排泄单纯靠肾脏。

东京药科大学等机构的一个联合研究小组研究发现，在尿酸排泄中发挥“水泵”作用的“ABCG2”蛋白质在肾脏、小肠和大肠内都发挥作用。对实验鼠进行的研究中，研究人员在实验鼠肾脏排出尿酸机能不变的情况下，人为抑制肠道中“ABCG2”蛋白质的产生，降低肠道排出尿酸的功能，结果尿酸在实验鼠体内蓄积。研究人员认为，肾脏承担了三分之二的尿酸排泄，其余部分则由肠道承担。

研究小组成员、东京药科大学教授市田公美指出，这是首次发现痛风和肠道之间的密切关系，这可能有助于发现新的预防痛风方法或者开发相关治疗药物。（生物谷 bioon.com）

doi:10.1038/ncomms1756
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Decreased extra-renal urate excretion is a common cause of hyperuricemia

Kimiyoshi Ichida,Hirotaka Matsuo,Tappei Takada,Akiyoshi Nakayama,Keizo Murakami,Toru Shimizu,Yoshihide Yamanashi,Hiroshi Kasuga,Hiroshi Nakashima,Takahiro Nakamura,Yuzo Takada,Yusuke Kawamura,Hiroki Inoue,Chisa Okada,Yoshitaka Utsumi et al

ABCG2, also known as BCRP, is a high-capacity urate exporter, the dysfunction of which raises gout/hyperuricemia risk. Generally, hyperuricemia has been classified into urate 'overproduction type' and/or 'underexcretion type' based solely on renal urate excretion, without considering an extra-renal pathway. Here we show that decreased extra-renal urate excretion caused by ABCG2 dysfunction is a common mechanism of hyperuricemia. Clinical parameters, including urinary urate excretion, are examined in 644 male outpatients with hyperuricemia. Paradoxically, ABCG2 export dysfunction significantly increases urinary urate excretion and risk ratio of urate overproduction. Abcg2-knockout mice show increased serum uric acid levels and renal urate excretion, and decreased intestinal urate excretion. Together with high ABCG2 expression in extra-renal tissues, our data suggest that the 'overproduction type' in the current concept of hyperuricemia be renamed 'renal overload type', which consists of two subtypes—'extra-renal urate underexcretion' and genuine 'urate overproduction'—providing a new concept valuable for the treatment of hyperuricemia and gout.