基于PDZK1/URAT1/NLRP3轴探讨猫须草治疗高尿酸血症的作用机制研究

高尿酸血症(HUA)危害严重，中药猫须草抗HUA优势明确。我们前期构建符合临床的湿热内蕴型HUA，发现该模型状态下PDZK1/URAT1可显著表达，且与炎症因子的释放呈正相关；猫须草可调控PDZK1/URAT1的表达和抗炎发挥降尿酸药效。基于以上研究，我们提出假说:“HUA是机体湿热内蕴于肾引起PDZK1/URAT1/NLRP3轴调控尿酸障碍的代谢性疾病；猫须草通过激活PDZK1介导的尿酸转运体URAT1，促进肾脏尿酸排泄以达“祛湿”，抑制NLRP3/IL-1β通路，减少炎症因子释放以达“清热”，从而发挥“清热祛湿”降尿酸药效”。研究从动物、细胞、分子三个层面，结合PRM靶向蛋白组学、siRNA基因敲低、靶向垂钓等技术，在系统探讨湿热内蕴型HUA病理基础上，阐释猫须草抗HUA的作用机制。本项目不仅为HUA的中医药防治提供新靶标，也为中药传统功效的现代化研究提供新思路。

The harm of hyperuricemia (HUA) is serious, and the anti-HUA advantage of the national medicine Clerodendranthus spicatus (Thunb.) C. Y. Wu (C. spicatus) is clear. We previously constructed a clinical HUA with endogenous damp heat, and found that PDZK1/URAT1 can be significantly expressed in this model state, and it is positively correlated with the release of inflammatory factors; C. spicatus can reduce uric acid by regulating the expression of PDZK1/URAT1 and anti-inflammatory. Based on the above research, we propose a hypothesis, "HUA is a metabolic disease caused by the body's "damp heat" in the kidney, which causes the PDZK1/URAT1/NLRP3 axis to regulate uric acid disorders ; C. spicatus inhibits the NLRP3/IL-1β pathway, reduces the release of inflammatory factors to achieve "clearing heat", activates the uric acid transport mediated by PDZK1 skeleton protein, and promotes the excretion of uric acid in the kidney to "remove dampness", thereby playing the role of "clearing heat and removing dampness". "Uric acid-lowering efficacy". Research from the three levels of animals, cells and molecules, using PRM-targeted proteomics, siRNA gene knockdown, targeted fishing and other technologies to systematically explore the damp-heat intrinsic type of HUA, explain the target and mechanism of anti-HUA of C. spicatus. This study not only provides experimental basis for the prevention and treatment of HUA with traditional Chinese medicine, but also provides new ideas for modern research on the traditional efficacy of traditional Chinese medicine.