基于ABCG2靶向分子轴探讨尿酸盐肾沉积机制及中药干预研究

尿酸盐肾沉积是关联高尿酸血症及痛风的关键病理环节，具先发性（早于关节）、危害大（脏器损伤）特点。但其机制不清，临床抗沉积药缺如，其防治研究亟待开展。尿酸代谢紊乱等慢性进展性疾病的防治是中医药的优势领域。.前期研究发现尿酸盐肾沉积是高血尿酸与低度炎症共同作用结果，转运体ABCG2可同时介导尿酸外排与炎症反应，提示ABCG2可能是抗沉积的关键。结合非编码RNA基因调控网络干预ABCG2表达报道，本次以中药菊苣为例，提出假说：尿酸盐肾沉积可能与LncRNA H19/miR-519c/ABCG2 mRNA下调ABCG2表达，干扰ABCG2介导尿酸转运及炎症反应有关；菊苣干预ABCG2靶向分子轴，改善尿酸排泄及低度炎症可能是其抗尿酸盐肾沉积机制。.采用多学科手段，应用本组创建动物模型，体内外逐层明晰尿酸盐肾沉积机制及中药效用特点，以奠定其防治研究基础，借鉴中药抗沉积药效评价，助力抗沉积药物研发。

Renal urate deposition, which is characterized by pre-existing (earlier than joint) and seriously harmful (organ injury), may be an essential pathological link between hyperuricemia and gout. However, its pathogenesis is unclear with no drugs available. Traditional Chinese Medicine is good at intervening in chronic metabolic diseases such as urate metabolism disorder..Previous studies found that renal urate deposition resulted from both high blood uric acid and low-grade inflammation. Combined with the function of uric acid efflux and anti-inflammation mediated by ABCG2, it suggests that ABCG2 may be the key point for anti-urate deposition. According to the report that the gene regulatory networks linked by non-coding RNA could regulate ABCG2 expression, the present study takes the chicory (Cichorium intybus L.) as an example and put forward the hypothesis. It supposes that renal urate deposition may be caused by the disorder of urate transport and inflammation mediated by ABCG2 expression down-regulated with LncRNA H19/miR-519c/ABCG2 mRNA. Chicory could regulate the ABCG2 targeting molecular axis to promote uric acid efflux and improve low-grade inflammation, which contributes to anti-urate deposition in the kidney. .Based above, the present study will use the animal model established by our group and carry out experiments in vitro and in vivo with multidisciplinary approaches to explore the pathological mechanism and medicinal treatment of renal urate deposition. We hope our work will provide value for the treatment of renal urate deposition by Traditional Chinese Medicine.