高尿酸血症（HUA）已成为严重的公共卫生问题。我们研究发现亚健康湿热证是预防HUA的重要窗口，但其机制不明。基于前期研究结果推测：亚健康湿热证肠道菌群失调可能激活炎症小体NLRP3，引起巨噬细胞分泌IL-1β、TNF-α炎症因子增多，诱导尿酸代谢相关基因表达异常，导致血尿酸升高，其又可以活化炎症小体NLRP3而形成恶性循环，从而促进HUA的发病过程。本项目拟运用多学科交叉优势，充分发挥中医治未病思想，以亚健康湿热证人群为切入点，首先进行前瞻性队列研究结合临床试验，明确四妙丸对亚健康湿热证HUA发病的影响，多组学联合分析亚健康湿热证肠道菌群与尿酸代谢的相关性；其次利用无菌小鼠和基因敲除小鼠，明确亚健康湿热证肠道菌群对尿酸代谢的影响及炎症小体NLRP3的调节作用；最后采用体外细胞共培养体系，阐明亚健康湿热证肠道菌群介导的“炎症因子—尿酸代谢”crosstalk机制，揭示湿热证的生物学基础。

Hyperuricemia (HUA) has become a serious public health problem. We found that the damp-heat syndrome of sub-health state is an important window for prevention of HUA, but its mechanism remains unclear. Based on our previous research results, it was speculated that dysbacteriosis with damp-heat syndrome of sub-health may activate NLRP3 inflammasome and cause macrophage secretion of IL-1β and TNF-α, increasing the expression of uric acid metabolism-related genes, and lead to elevated uric acid. Then it can activate the NLRP3 inflammasome pathway and form a vicious cycle, promoting the pathogenesis of HUA. This project intends to use multidisciplinary crossover advantages to give full use to the idea of treating pro-diseases in traditional Chinese medicine. Taking the damp-heat syndrome of the sub-healthy population as the starting point: First of all, clinical trials were conducted to observe the effect of Simiao Pills on of uric acid levels of damp-heat syndrome in sub-health state and investigate the relationship between intestinal microbiota and uric acid metabolism with damp-heat syndromes of sub-healthy using a joint analysis; Secondly, sterile mice and knockout mice were used to determine the effect of the uric acid production and excretion with damp-heat syndrome of sub-health and regulation of NLRP3 inflammasome; Finally, in vitro cell culture system was used to elucidate the crosstalk mechanism of “inflammasome - uric acid metabolism” mediated by intestinal flora with damp heat syndrome of sub-healthy, which is of great significance for the prevention of HUA.