高尿酸血症（Hyperuricemia, HUA）作为一种患病率逐年攀升的代谢异常疾病，能够诱发痛风、肾功能不全等病症，其潜在危害不容忽视。基于中药配方的保健食品在治疗高尿酸血症方面表现出安全性强、接受度高等独特优势，然而，对其的研究和开发却远远不足。

薏苓草方由30 g薏苡仁，20 g茯苓，15 g车前草，20 g山药，10 g红花，15 g葛根构成，是基于国医大师传承人多年临床经验提出、符合中医理论、证型明确、药简力宏的药食两用新组方，可有效缓解高尿酸血症。但其可能的药效机制尚需探明。本论文在酵母膏和氧嗪酸钾诱导的高尿酸血症大鼠模型上，连续灌胃薏苓草方水提液28天，采用别嘌醇作为阳性对照，观察薏苓草方对大鼠血尿酸、Alanine aminotransferase (ALT)、 Aspartate aminotransferase (AST)、Creatinine (CRE)、Blood urea nitrogen (BUN)、腺苷脱氨酶（Adenosine deaminase, ADA）、黄嘌呤氧化酶（Xanthine oxidase, XOD）以及肾脏尿酸排泄分数（Fractional excretion of uric acid, FEUA）的影响，通过quantitative Real-time PCR (qRT-PCR) 对网络药理学预测的肾脏尿酸转运蛋白靶点进行验证，深入探讨了组方对高尿酸血症大鼠的降尿酸作用及其机制。取得的主要成果如下：

（1）证实了薏苓草方水提取物对HUA大鼠的降尿酸作用。水提液在给药第21天开始出现明显的降尿酸作用（p<0.01）。相比模型组，水提液能够降低血清BUN（p<0.001）、CRE浓度（p<0.05），减轻肝脏病理损伤和肝脏水肿，因此组方一定程度上能够缓解造模剂引发的肝、肾损伤。薏苓草方能显著抑制血清和肝脏组织中尿酸合成的关键酶ADA和XOD的活性，增加了大鼠24h尿尿酸排泄量（p<0.05）和肾脏尿酸排泄分数（p<0.001）。

（2）预测了薏苓草方水提取物降尿酸的潜在机制并验证了水提取物促进肾脏尿酸排泄的作用靶点。共筛选出薏苓草方活性成分137个和作用靶点729个，获取疾病靶点291个。通过构建的中药-成分-靶点复合网络图，筛选出PTGS2、NCOA2、TNF、XDH、PPARG、ALDH2、SLC6A3等薏苓草方治疗高尿酸血症的关键靶点和ABCG2（ABCG2）、SLC22A12（URAT1）、SLC22A6（OAT1）等薏苓草方调节尿酸转运相关的靶点。通过GO、KEGG富集，预测薏苓草方治疗HUA的生物途径可能包括影响免疫系统和炎症反应、MAPK信号通路、脂多糖的细胞应答、影响细胞内外的分子相互作用以及对特定疾病相关信号通路的调节。经qRT-PCR验证，组方增加肾脏尿酸排泄可能通过是降低大鼠肾脏URAT1 mRNA水平（p<0.01），并提高大鼠ABCG2（p<0.05）和OAT1 mRNA（p<0.05）水平实现的。

（3）利用UPLC-Q-TOF-MS/MS指认了水提液中的30个化学成分，主要是异黄酮、查尔酮、苯丙烷类糖苷类成分。经标准品准确指认了羟基红花黄色素A、葛根素、大豆苷、3’-羟基葛根素、3’-甲氧基葛根素、大车前苷，并选择羟基红花黄色素A、葛根素为指标性成分建立了水提液的含量测定方法。为组方药效物质基础和质控研究定了坚实的实验基础。

综上所述，本实验已成功证实了薏苓草方在降低尿酸方面的显著药效，作用机制可能与通过抑制ADA和XOD酶活性减少尿酸生成，调节大鼠肾脏尿酸转运蛋白ABCG2、URAT1、OAT1的表达从而抑制近端肾小管对尿酸的重吸收、促进尿酸排泄有关。本研究对该方的临床应用和产品开发具有重要意义，这一组方有望为治疗高尿酸血症提供新的治疗策略。

Hyperuricemia (HUA), as a metabolic disorder with a rising incidence rate each year, can induce diseases such as gout and renal insufficiency, and its potential hazards cannot be ignored. Health foods based on traditional Chinese medicine formulas have shown unique advantages in the treatment of hyperuricemia, such as strong safety and high acceptance. However, research and development in this area are still insufficient.

The yilingcao formula (YLC) in this study consists of 30 g of Coix seed (Coix lacryma-jobi L.), 20 g of Poria cocos (Poria cocos (Schw.) Wolf), 15 g of Plantaginis herba (Plantago asiatica L.), 20 g of Yam (Dioscorea opposita Thunb.), Kudzu (Pueraria lobate (Willd.) Ohwi.), and 10 g of Safflower (Carthamus tinctorius L.). It is a new medicinal and edible formula proposed based on the clinical experience of inheritors of traditional Chinese medicine masters for many years. It conforms to the theories of traditional Chinese medicine, with clear syndrome differentiation and extensive use of herbs. It can effectively alleviate hyperuricemia. However, its potential pharmacological mechanism still needs to be elucidated.

In this study, the YLC water extract was administered orally to hyperuricemia rats induced by yeast paste and potassium oxonate for 28 days. Allopurinol was used as a positive control. The effects of the YLC on serum uric acid, ALT, AST, CRE, BUN, ADA, XOD, and renal uric acid excretion fraction in rats were observed. qRT-PCR was used to verify the renal uric acid transport protein targets predicted by network pharmacology. The study thoroughly investigated the uric acid-lowering effect and mechanism of the YLC in hyperuricemia rats. The main findings are as follows:

(1) The water extract of the YLC was confirmed to have a uric acid-lowering effect on HUA rats. The uric acid-lowering effect of the water extract became significant on the 21st day of administration (p<0.01). Compared with the model group, the water extract could reduce serum BUN (p<0.001) and CRE concentration (p<0.05), alleviate liver pathological damage and liver edema, thus alleviating the liver and kidney damage induced by the modeling agent to a certain extent. The YLC significantly inhibited the activity of key enzymes ADA and XOD involved in uric acid synthesis in serum and liver tissues, increased 24 h urine uric acid excretion in rats (p<0.05), and renal uric acid excretion fraction (FEUA) (p<0.001).

(2) The potential mechanism of uric acid reduction by the water extract of the YLC was predicted and the target of promoting renal uric acid excretion by the water extract was verified. A total of 137 active ingredients and 729 target proteins of the YLC were screened, and 291 disease targets were obtained. Through the constructed Chinese medicine-ingredient-target composite network diagram, key targets of the YLC for treating hyperuricemia such as PTGS2, NCOA2, TNF, XDH, PPARG, ALDH2, and SLC6A3, as well as targets regulating uric acid transport such as ABCG2, SLC22A12 (URAT1), and SLC22A6 (OAT1) were selected. Through GO and KEGG enrichment, it was predicted that the biological pathways of the YLC in treating HUA may include affecting the immune system and inflammatory response, MAPK signaling pathway, lipopolysaccharide cell response, affecting molecular interactions inside and outside cells, and regulating specific disease-related signaling pathways. qRT-PCR verification showed that the YLC increased renal uric acid excretion may be achieved by reducing the mRNA levels of URAT1 in rat kidneys (p<0.01), and increasing the mRNA levels of ABCG2 (p<0.05) and OAT1 (p<0.05) in rats.

(3) Thirty chemical components were identified in the water extract by UPLC-Q-TOF-MS/MS, mainly flavonoids, chalcones, and phenylpropane glycosides. Hydroxy safflower yellow A, puerarin, daidzin, 3'-hydroxy puerarin, 3'-methoxy puerarin, and plantain glucoside were accurately identified by standard substances, and hydroxy safflower yellow A and puerarin were selected as index components to establish a method for determining the content of the water extract. This provides a solid experimental basis for the study of the pharmacological substance basis and quality control of the YLC.

In summary, this experiment has successfully demonstrated the significant efficacy of the YLC in reducing uric acid, and its mechanism of action may involve reducing uric acid production by inhibiting ADA and XOD enzyme activities, regulating the expression of renal uric acid transport proteins ABCG2, URAT1, and OAT1 in rats, thereby inhibiting proximal tubular reabsorption of uric acid and promoting uric acid excretion. This study is of great significance for the clinical application and product development of this formula, and this formula is expected to provide a new treatment strategy for hyperuricemia.