Simiao San（SmS）是一种著名的中药方剂，临床上被用于治疗高尿酸血症（HUA）患者，但它降低尿酸（UA）和抑制炎症的作用机制仍需进一步探究。本研究旨在探讨SmS对HUA小鼠UA代谢和肾脏损伤的影响及其潜在机制。使用草酸钾和次黄嘌呤联合给药构建HUA小鼠模型，通过ELISA或生化分析测定SmS对UA、黄嘌呤氧化酶（XOD）、肌酐（CRE）、血肌酐氮（BUN）、白细胞介素-10（IL-10）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的影响。使用苏木精伊红染色（H＆E）观察HUA小鼠的肾脏病理变化。通过Western blot和/或免疫组化染色检测有机阴离子转运体1（OAT1）、重组尿酸转运体1（URAT1）、葡萄糖转运体9（GLUT9）、核苷酸结合域和亮氨酸富含重复的炎症体3（NLRP3）、剪切-Caspase 1、凋亡相关斑点样蛋白（ASC）、核因子-kappa B（NF-κB）、IL-6、Janus 激酶2（JAK2）、磷酸化（P）-JAK2、信号转导和转录激活因子3（STAT3）、P-STAT3、细胞因子信号抑制蛋白3（SOCS3）的表达水平。使用HPLC-MS方法鉴定了SmS的主要成分。结果发现，HUA小鼠血清UA、BUN、CRE、XOD和尿白蛋白/肌酐比值（UACR）升高，尿液UA和CRE含量降低，同时引起小鼠的炎症反应，包括血清IL-1β、IL-6和TNF-α水平升高，肾脏中URAT1，GULT9，NLRP3，ASC，Cleaved-Caspase1，P-JAK2/JAK2，P-STAT3/STAT3和SOCS3表达增加，血清IL-10水平和肾脏OAT1表达降低，肾脏病理组织结构混乱。与之相反，SmS干预可以逆转这些变化。因此，SmS可以缓解HUA小鼠的高尿酸血症和肾脏炎症。这些变化的作用机制可能与限制NLRP3炎症体和JAK2 / STAT3信号通路有关。版权所有©2023 Elsevier B.V.发行。

Simiao San (SmS), a famous traditional Chinese formula, is clinically used to treat patients with hyperuricemia (HUA). However, its mechanism of action on lowering uric acid (UA) and inhibiting inflammation still deserves further investigation.To examine the effect and its possible underlying mechanism of SmS on UA metabolism and kidney injury in HUA mouse.The HUA mouse model was constructed with the combined administration of both potassium oxalate and hypoxanthine. The effects of SmS on UA, xanthine oxidase (XOD), creatinine (CRE), blood urea nitrogen (BUN), interleukin-10 (IL-10), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by ELISA or biochemical assay. Hematoxylin and eosin (H&E) was used to observe pathological alterations in the kidneys of HUA mice. The expression levels of organic anion transporter 1 (OAT1), recombinant urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), nucleotide binding domain and leucine rich repeat pyrin domain containing 3 (NLRP3), Cleaved-Caspase 1, apoptosis-associated speck like protein (ASC), nuclear factor kappa-B (NF-κB), IL-6, janus kinase 2 (JAK2), phosphor (P)-JAK2, signal transducers and activators of transcription 3 (STAT3), P-STAT3, suppressor of cytokine signaling 3 (SOCS3) were examined by Western blot and/or immunohistochemical (IHC) staining. The major ingredients in SmS were identified by a HPLC-MS assay.HUA mouse exhibited an elevation in serum levels of UA, BUN, CRE, XOD, and the ratio of urinary albumin to creatinine (UACR), and a decline in urine levels of UA and CRE. In addition, HUA induces pro-inflammatory microenvironment in mouse, including an increase in serum levels of IL-1β, IL-6, and TNF-α, and renal expressions of URAT1, GULT9, NLRP3, ASC, Cleaved-Caspase1, P-JAK2/JAK2, P-STAT3/STAT3, and SOCS3, and a decrease in serum IL-10 level and renal OAT1 expression as well as a disorganization of kidney pathological microstructure. In contrast, SmS intervention reversed these alterations in HUA mouse.SmS could alleviate hyperuricemia and renal inflammation in HUA mouse. The action mechanisms behind these alterations may be associated with a limitation of the NLRP3 inflammasome and JAK2/STAT3 signaling pathways.Copyright © 2023. Published by Elsevier B.V.