膨腹海马乙醇提取物改善小鼠高尿酸血症的作用机制

doi:10.7506/spkx1002-6630-20250922-171

食品科学 ›› 2026, Vol. 47 ›› Issue (5): 162-173.doi: 10.7506/spkx1002-6630-20250922-171

• 营养卫生 • 上一篇

膨腹海马乙醇提取物改善小鼠高尿酸血症的作用机制

张嘉媛，冯碧芸，李玲燕，杨欣慧，孔亚玲，王苏萍，李明，许光辉

（1.厦门市健康医疗大数据中心（厦门市医药研究所），厦门市天然药物研究与开发重点实验室，福建厦门 361008；2.福建中医药大学药学院，福建福州 350122）

发布日期:2026-04-13
基金资助:
厦门市卫生健康高质量发展科技计划项目（2024GZL-CX43）；厦门市自然科学基金项目（3502Z202373139）；厦门市扶持中医药发展专项（XWZY-2025-0536；XWZY-2025-0317）；福建省医学创新课题（2024CXB027）

Molecular Mechanism of Ethanol Extract from Hippocampus abdominalis in Improving Hyperuricemia in Mice

ZHANG Jiayuan, FENG Biyun, LI Lingyan, YANG Xinhui, KONG Yaling, WANG Suping, LI Ming, XU Guanghui

(1. Xiamen Health and Medical Big Data Center (Xiamen Medicine Research Institute), Xiamen Key Laboratory of Natural Medicine Research and Development, Xiamen 361008, China; 2. College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China)

Published:2026-04-13

摘要/Abstract

摘要： 目的：研究膨腹海马乙醇提取物对小鼠高尿酸血症的作用与分子机制。方法：利用高效化学同位素双标记技术检测膨腹海马乙醇提取物及小鼠血清中的化学成分；利用氧嗪酸钾联合次黄嘌呤诱导建立小鼠高尿酸血症模型；使用商品化生化检测试剂盒检测小鼠血清中尿酸、肌酐、尿素氮水平以及肝脏组织黄嘌呤氧化酶的活性；利用苏木素和伊红染色检测分析小鼠肾脏损伤水平；利用Western blot方法检测蛋白质表达水平；利用高通量测序方法检测分析小鼠肠道菌群变化。结果：对膨腹海马乙醇提取物及相关小鼠血清进行化学物质检测鉴定，发现膨腹海马乙醇提取物共包含1 174 种化合物，主要涵盖肽类、氨基酸类、羧酸类、脂肪酸类等。相对于正常小鼠及高尿酸血症小鼠，海马乙醇提取物处理组小鼠血清中独有并且存在于膨腹海马乙醇提取物中的化合物共8 个（酪氨酰-脯氨酸、异亮氨酰-丝氨酸、苏氨酰-丙氨酸、色氨酰-丝氨酸、前列腺素D2、罗汉松树脂酚、4-吡哆酸、柠檬酸），它们可能作为膨腹海马乙醇提取物的入血成分。与模型组小鼠相比较，膨腹海马乙醇提取物处理组小鼠血清尿酸水平显著下降，说明膨腹海马乙醇提取物显著抑制高尿酸血症小鼠血清中尿酸水平。同时，膨腹海马乙醇提取物显著抑制高尿酸血症小鼠血清中肌酐、尿素氮水平以及肾脏损伤水平。以上结果表明膨腹海马乙醇提取物改善小鼠高尿酸血症，保护肾功能。膨腹海马乙醇提取物抑制高尿酸血症小鼠肝脏组织中黄嘌呤氧化酶的水平及肾脏组织中尿酸重吸收蛋白（尿酸盐转运蛋白1、葡萄糖转运蛋白9）的表达水平，促进肾脏组织中尿酸排泄蛋白（ATP结合盒转运蛋白G2、有机阴离子转运蛋白1、有机阴离子转运蛋白3）的表达水平，表明膨腹海马乙醇提取物可能通过影响尿酸生成、尿酸排泄和重吸收层面调控小鼠血尿酸水平。膨腹海马乙醇提取物显著改变了高尿酸血症小鼠肠道部分菌群的丰度，使其丰度倾向于正常小鼠，说明膨腹海马乙醇提取物可能通过重塑肠道微生态调控血尿酸水平。结论：膨腹海马乙醇提取物可以通过调控黄嘌呤氧化酶活性、尿酸转移蛋白表达、肠道菌群等途径显著改善小鼠高尿酸血症。

关键词: 膨腹海马；高尿酸血症；尿酸排泄蛋白；尿酸重吸收蛋白；肠道菌群

Abstract: Objective: To study the effect and molecular mechanism of ethanol extract from Hippocampus abdominalis on hyperuricemia in mice. Methods: The chemical components in the ethanol extract and the mouse serum were analyzed using high performance chemical isotope labeling (HP-CIL) technology. A mouse model of hyperuricemia was established by co-administration of potassium oxazinate and hypoxanthine. Serum levels of uric acid, creatinine, and uric acid nitrogen, as well as hepatic xanthine oxidase activity, were detected using commercial detection kits. HE staining was used to detect renal injury in mice. Western blot was used to detect protein expression levels. High throughput sequencing was used to analyze the changes in the gut microbiota in mice. Results: Chemical analysis identified 1 174 compounds in the hippocampal extract, among which peptides, amino acids, carboxylic acids, and fatty acids were the main ones. Eight compounds (tyrosyl-proline, isoleucyl-serine, threoninyl-alanine, tryptophyl-serine, prostaglandin D2, mataric acid, 4-pyridoxic acid, and citric acid) were exclusively present in the serum of hippocampal extract-treated mice compared with normal and hyperuricemic mice and these compounds were also were found in the extract, suggesting their absorption into the blood circulation. Compared with the model mice, the extract significantly reduced serum uric acid levels. It also significantly reduced serum creatinine, uric acid nitrogen levels and alleviated renal injury, indicating renal protection. The ethanol extract inhibited hepatic xanthine oxidase and suppressed the renal expression of uric acid reabsorption transporters (URAT1 and GLUT9), while promoting the expression of uric acid excretion transporters (ABCG2, OAT1, and OAT3) in kidney tissue, indicating that H. abdominalis extract may regulate the level of blood uric acid in mice by affecting uric acid production, excretion and reabsorption. Furthermore, the extract significantly modulated the abundance of gut microbiota in hyperuricemic mice, restoring it to nearly normal levels. This demonstrates that the extract can regulate blood uric acid levels by remodeling intestinal microecology. Conclusion: H. abdominalis ethanol extract significantly ameliorates hyperuricemia in mice by regulating xanthine oxidase activity, uric acid transporter expression, and the gut microbiota.

Key words: Hippocampus abdominalis; hyperuricemia; uric acid excretion proteins; uric acid reabsorption proteins; gut microbiota

中图分类号:

R151.2

张嘉媛，冯碧芸，李玲燕，杨欣慧，孔亚玲，王苏萍，李明，许光辉. 膨腹海马乙醇提取物改善小鼠高尿酸血症的作用机制[J]. 食品科学, 2026, 47(5): 162-173.

ZHANG Jiayuan, FENG Biyun, LI Lingyan, YANG Xinhui, KONG Yaling, WANG Suping, LI Ming, XU Guanghui. Molecular Mechanism of Ethanol Extract from Hippocampus abdominalis in Improving Hyperuricemia in Mice[J]. FOOD SCIENCE, 2026, 47(5): 162-173.

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膨腹海马乙醇提取物改善小鼠高尿酸血症的作用机制

Molecular Mechanism of Ethanol Extract from Hippocampus abdominalis in Improving Hyperuricemia in Mice

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