天然产物研究与开发 ›› 2026, Vol. 38 ›› Issue (8): 1640-1651.doi: 10.16333/j.1001-6880.2026.8.002 cstr: 32307.14.1001-6880.2026.8.002

• 研究论文 • 上一篇    下一篇

牛蒡根多糖改善小鼠慢性高尿酸血症及肾损伤的作用机制研究

周在富1,王玉霞2*,陈道洪3,任洪波3,林泉松3   

  1. 1重庆化工职业学院,重庆 401220;2重庆医药高等专科学校,重庆 4013313重庆科瑞制药(集团)有限公司,重庆 400060
  • 出版日期:2026-08-27 发布日期:2026-08-26
  • 基金资助:
    重庆市科技攻关计划(CSTC2011ggc10006-07)

Mechanisms of Arctium lappa root polysaccharides in ameliorating chronic hyperuricemia and renal injury in mice

ZHOU Zai-fu1,WANG Yu-xia2*,CHEN Dao-hong3,REN Hong-bo3,LIN Quan-song3   

  1. 1Chongqing Chemical Industry Vocational College,Chongqing 401220,China;2Chongqing Medical and Pharmaccutical College,Chongqing 401331,China;3Chongqing Kerui Pharmaceutical (Group) Co.,Ltd.,Chongqing 400060,China
  • Online:2026-08-27 Published:2026-08-26

摘要:

探讨牛蒡根多糖(Arctium lappa root polysaccharides,ALRP)对腺嘌呤联合高嘌呤饮食诱导的慢性高尿酸血症(hyperuricemia,HUA)小鼠的治疗作用及其潜在分子机制。采用腺嘌呤联合高嘌呤饮食诱导建立HUA小鼠模型,将60只SPF级雄性ICR小鼠随机分为正常对照组、模型组、非布司他阳性对照组、ALRP低剂量组和ALRP高剂量组,连续灌胃给药28 d。测定小鼠体重、肾脏指数,检测血清和尿液中尿酸(uric acid,UA)、肌酐(creatinine,Cr)水平及尿酸清除率(uric acid clearance rate,UACR)、尿酸/肌酐比值(U/C);测定肾脏组织匀浆中氧化应激和炎症因子水平;HE染色观察肾脏组织病理学变化;通过宏基因组测序分析肠道菌群结构变化,并采用靶向代谢组学检测粪便胆汁酸含量。结果表明,与模型组相比,ALRP各剂量组小鼠体重显著增加,肾脏指数显著降低;血清UA、Cr水平显著下降,UACR显著升高,尿液U/C显著升高(P<0.05或P<0.01);肾脏组织氧化应激水平显著降低,炎症因子水平显著下降(P<0.05或P<0.01);肾脏组织病理学评分显著改善,肾小管损伤和间质炎症程度减轻(P<0.05或P<0.01);肠道菌群α多样性增加,β多样性显著改变,有益菌丰度上升,有害菌丰度下降;粪便中次级胆汁酸含量显著增加(P<0.05或P<0.01)。综上,ALRP对慢性HUA小鼠具有显著的肾脏保护作用,其机制可能与降低血尿酸水平、改善肾脏氧化应激和炎症状态、调节肠道菌群结构及促进胆汁酸代谢有关。

关键词: 牛蒡根多糖, 慢性高尿酸血症, 肾脏保护, 肠道菌群, 胆汁酸代谢

Abstract:

This study aimed to investigate the therapeutic effects of Arctium lappa root polysaccharides (ALRP) on chronic hyperuricemia (HUA) mice induced by adenine combined with a high-purine diet and to explore the underlying molecular mechanisms. A HUA mouse model was established using this induction approach, and 60 SPF-grade male ICR mice were randomly divided into a normal control group, a model group, a positive control group (febuxostat), a low-dose ALRP group, and a high-dose ALRP group, with intragastric administration for 28 consecutive days. Body weight and renal index were measured, and serum and urinary levels of uric acid (UA) and creatinine (Cr), along with uric acid clearance rate (UACR) and the uric acid-to-creatinine ratio (U/C), were determined. Oxidative stress markers and inflammatory cytokine levels were assessed in renal tissue homogenates, and histopathological changes in kidney tissue were observed by HE staining. Gut microbiota structural changes were analyzed by metagenomic sequencing, and fecal bile acid content was measured by targeted metabolomics. The results showed that, compared with the model group, mice in both ALRP dose groups exhibited significantly increased body weight and significantly reduced renal index; serum UA and Cr levels were significantly decreased, UACR was significantly elevated, and urinary U/C ratio was significantly increased (P<0.05 or P<0.01); renal oxidative stress and inflammatory cytokine levels were significantly reduced (P<0.05 or P<0.01); histopathological scores of kidney tissue were significantly improved, with alleviated renal tubular damage and interstitial inflammation (P<0.05 or P<0.01); gut microbiota α-diversity was increased, β-diversity was significantly altered, the abundance of beneficial bacteria was elevated, and that of harmful bacteria was decreased; and fecal secondary bile acid content was significantly increased (P<0.05 or P<0.01). In conclusion, ALRP exert significant renoprotective effects in chronic HUA mice, and the underlying mechanisms may be related to the reduction of serum uric acid levels, improvement of renal oxidative stress and inflammatory status, modulation of gut microbiota composition, and promotion of bile acid metabolism.

Key words:

Arctium lappa root polysaccharides, chronic hyperuricemia, renal protection, gut microbiota, bile acid metabolism

中图分类号:  R285.5 TS201.4