体内尿酸排泄不足是高尿酸血症的主要诱因，而尿酸的排泄依赖于肠道与肾脏中尿酸盐转运体SLC22A12和SLC2A9的共同作用，靶向尿酸转运体的药物是近年来降尿酸药物研究的热点。本课题前期研究发现高尿酸血症动物肠道代谢产物短链脂肪酸（SCFAs）较正常动物明显减少，SCFAs在体内外能通过同时抑制SLC22A12和SLC2A9的尿酸转运活性降低高尿酸血症小鼠体内尿酸水平，其作用机制与肠道与肾脏中尿酸转运活性有关。本课题基于“肠-肾轴”理论研究肠道来源的SCFAs对肠-肾组织尿酸排泄过程的影响，通过建立过表达SLC22A12和SLC2A9体外细胞模型、高尿酸血症小鼠模型等研究SCFAs对肠-肾中尿酸转运蛋白SLC22A12和SLC2A9的作用，并阐明其分子机制，为研发以SLC22A12和SLC2A9为双靶点的新型降尿酸药物提供设计思路，同时为高尿酸血症的防治提供新的方法。

Insufficient excretion is the dominant cause of hyperuricaemia. The uric acid in the body is excreted by the kidney and intestine based on the urate transporters SLC22A12 and SLC2A9. In recent years, these urate transporters are recognized to be direct targets for drugs to treat patients with hyperuricemia. Our previous experiments found that the SCFAs contents in the feces of hyperuricemic animals were significantly decreased compared to the normal controls. Further in vitro and in vivo studies showed that SCFAs significantly reduced the serum uric acid levels via inhibition of GLUT9 and URAT1 in mice with hyperuricemia. Therefore, the study aims to explore the effects of SCFAs on the renal or extra-renal urate excretion in hyperuricemic mice based on the “gut-kidney” axis. We would investigate the effects of SCFAs on the urate transporters SLC22A12 and SLC2A9 expressed in the intestine and kidney and detect their effects on the serum uric acid levels in mice with hyperuricaemia in vitro and in vivo and further clarify the underlying molecular mechanisms, aiming to provide new ideas for the design of dual inhibitors of GLUT9 and URAT1 as novel uricosurics and also provide a new method for the prevention and treatment of hyperuricemia.