Kushiyama Akifumi, Nakatsu Yusuke, Matsunaga Yasuka, Yamamotoya Takeshi, Mori Keiichi, Ueda Koji, Inoue Yuki, Sakoda Hideyuki, Fujishiro Midori, Ono Hiraku, Asano Tomoichiro
Division of Diabetes and Metabolism, Institute for Adult Disease, Asahi Life Foundation, 1-6-1 Marunouchi, Chiyoda-ku, Tokyo, Japan.
Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan.
Mediators Inflamm. 2016;2016:8603164. doi: 10.1155/2016/8603164. Epub 2016 Dec 14.
Uric acid (UA) is the end product of purine metabolism and can reportedly act as an antioxidant. However, recently, numerous clinical and basic research approaches have revealed close associations of hyperuricemia with several disorders, particularly those comprising the metabolic syndrome. In this review, we first outline the two molecular mechanisms underlying inflammation occurrence in relation to UA metabolism; one is inflammasome activation by UA crystallization and the other involves superoxide free radicals generated by xanthine oxidase (XO). Importantly, recent studies have demonstrated the therapeutic or preventive effects of XO inhibitors against atherosclerosis and nonalcoholic steatohepatitis, which were not previously considered to be related, at least not directly, to hyperuricemia. Such beneficial effects of XO inhibitors have been reported for other organs including the kidneys and the heart. Thus, a major portion of this review focuses on the relationships between UA metabolism and the development of atherosclerosis, nonalcoholic steatohepatitis, and related disorders. Although further studies are necessary, XO inhibitors are a potentially novel strategy for reducing the risk of many forms of organ failure characteristic of the metabolic syndrome.
尿酸（UA）是嘌呤代谢的终产物，据报道可作为一种抗氧化剂。然而，最近众多临床和基础研究方法揭示了高尿酸血症与多种疾病密切相关，尤其是那些构成代谢综合征的疾病。在本综述中，我们首先概述与尿酸代谢相关的炎症发生的两种分子机制；一种是尿酸结晶激活炎性小体，另一种涉及黄嘌呤氧化酶（XO）产生的超氧自由基。重要的是，最近的研究表明，XO抑制剂对动脉粥样硬化和非酒精性脂肪性肝炎具有治疗或预防作用，而这些疾病以前被认为与高尿酸血症至少没有直接关系。XO抑制剂对包括肾脏和心脏在内的其他器官也有这种有益作用。因此，本综述的主要部分聚焦于尿酸代谢与动脉粥样硬化、非酒精性脂肪性肝炎及相关疾病发展之间的关系。尽管还需要进一步研究，但XO抑制剂是降低代谢综合征特征性多种器官衰竭风险的一种潜在新策略。
