天然产物研究与开发 ›› 2026, Vol. 38 ›› Issue (3): 468-477.doi: 10.16333/j.1001-6880.2026.3.002 cstr: 32307.14.1001-6880.2026.3.002

• 研究论文 • 上一篇    下一篇

基于免疫炎症-肠道微生态探讨刺山柑果对高尿酸血症小鼠治疗作用

李阳杰1,刘心蕊2,梁  亮2,夏玲玲1,沈孝云1,丁  聪2*   

  1. 1新疆科技学院医学院,库尔勒 841000;2广西中医药大学赛恩斯新医药学院 广西壮瑶药重点实验室 壮瑶药协同创新中心,南宁 530200
  • 出版日期:2026-03-31 发布日期:2026-03-26
  • 基金资助:
    新疆维吾尔自治区“天池英才”引进计划;广西壮瑶药重点实验室(2014-32)(22-035-25);广西中医药大学赛恩斯新医药学院自治区级大学生创新创业项目(S202413643012)

Therapeutic effects of Capparis spinosa fruit in hyperuricemia mice based on the immune-inflammation-gut microbiota axis

LI Yang-jie1,LIU Xin-rui2,LIANG Liang2,XIA Ling-ling1,SHEN Xiao-yun1,DING Cong2*   

  1. 1College of Medicine Xinjiang University of Science and Technology,Korla 841000,China;2Faculty of Chinese Medicine Science,Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine Collaborative Innovation Center of Zhuang and Yao Ethnic Medicine,Guangxi University of Chinese Medicine,Nanning 530200,China
  • Online:2026-03-31 Published:2026-03-26

摘要:

基于免疫炎症-肠道微生态探究刺山柑果(Capparis spinosa fruit,CSF)对高尿酸血症(hyperuricemia,HUA)小鼠肾脏损伤、抗炎及对肠道菌群的影响。采用腹腔注射氧嗪酸钾(300 mg/kg)复制慢性HUA小鼠模型,将C57BL/6小鼠分为空白组、模型组、别嘌醇组(62.5mg/kg)和刺山柑果高剂量(400 mg/kg)、低剂量(200 mg/kg)组,每组10只;HE、Masson染色后小鼠肾脏组织的病理学变化;分别测定小鼠血清与尿液中尿酸(uric acid,UA)清除率;血清中肌酐(creatinine,Cr)、血尿素氮(blood urea nitrogen,BUN)和黄嘌呤氧化酶(xanthine oxidase,XOD)的水平;ELISA试剂盒检测小鼠血清中白细胞介素1β(interleukin-1β,IL-1β)、IL-10、核因子κB(nuclear factor kappa B,NF-κB)等炎性因子的水平;收集小鼠盲肠内容物,采用16S rRNA高通量测序法检测肠道菌群变化。动物实验结果表明,与空白组比较,肾脏组织病理学观察及肾功能损伤指标测定表明腹腔注射氧嗪酸钾可诱导慢性HUA模型,与模型组比较,CSF给药组干预后可明显改善HUA小鼠肾组织的病理病变,肾小管管壁变厚,管腔收缩,细胞空泡化减少,肾间质未见炎性细胞浸润,肾小管内部刷状缘结构恢复完整;HUA小鼠尿液及血清中UA、Cr、BUN、XOD等水平下降(P<0.01)、促炎因子IL-1β、NF-κB炎症因子的释放显著减少,抗炎因子IL-10表达水平显著升高(P<0.01);组间肠道菌群多样性丰富度和多样性发生显著改变,与空白组比较,模型组Muribaculaceae丰度增加,Prevotellaceae_UCG-003、PrevotellaBacteroides的丰度降低,经刺山柑果高剂量灌胃给药后相应菌群丰度均有效回调;相关性分析结果表明,Muribaculaceae、BacteroidesPrevotella菌群丰度与HUA肾损伤指标UA、Cr、BUN、XOD及炎性因子IL-1β、IL-10、NF-κB均呈现显著性相关,其中Muribaculaceae和Prevotella的丰度增加会导致HUA促炎因子IL-1β、NF-κB的释放增加,并降低抗炎因子IL-10的表达水平,加重了HUA的炎症病变,Bacteroides的丰度增加有益于HUA小鼠炎症的改善。CSF可能通过调节免疫炎症-肠道微生态紊乱而改善和治疗HUA,其作用机制与调控肠道菌群的多样性及改善差异菌群Muribaculaceae、PrevotellaBacteroides的丰度有关。

关键词: 刺山柑果, 免疫炎症, 肠道菌群, 高尿酸血症

Abstract:

This study aimed to investigate the effects of Capparis spinosa fruit (CSF) on gout in mice and its impact on gut microbiota. A hyperuricemia (HUA) injury model was established in C57BL/6 mice via intraperitoneal injection of potassium oxonate (300 mg/kg). The mice were divided into five groups (n = 10 per group): control, model, allopurinol, high-dose CSF (400 mg/kg), and low-dose CSF (200 mg/kg). Renal pathological changes were assessed using HE and Masson staining. Serum and urinary levels of uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN), and xanthine oxidase (XOD). Inflammatory cytokines, such as interleukin-1β (IL-1β), IL-10, nuclear factor kappa B (NF-κB) were detected using ELISA kits. Cecal contents were collected for 16S rRNA high-throughput sequencing to analyze changes in the gut microbiota. Following treatment group intervention, pathological damage in renal tissue of model mice was significantly ameliorated, with no inflammatory cell infiltration observed in the renal interstitium and restoration of the brush border structure within renal tubules. Levels of UA, Cr, BUN, and XOD in both serum and urine were significantly reduced (P<0.01). The release of pro-inflammatory factors (IL-1β and NF-κB) was markedly suppressed, while the expression of the anti-inflammatory factor IL-10 was significantly increased (P<0.01). Significant alterations in the richness and diversity of gut microbiota were observed among the groups. Compared with the control, the model exhibited an increased abundance of Muribaculaceae, and decreased abundances of Prevotellaceae_UCG-003, Prevotella, and Bacteroides. After treatment with high-dose CSF, these microbial imbalances were effectively reversed. Correlation analysis revealed that the abundances of Muribaculaceae, Bacteroides, and Prevotella were significantly associated with HUA-related renal injury indicators (UA, Cr, BUN, XOD) and inflammatory factors (IL-1β, IL-10, NF-κB). Specifically, increased abundances of Muribaculaceae and Prevotella were associated with elevated levels of pro-inflammatory factors IL-1β and NF-κB, reduced expression of IL-10, and aggravated inflammatory injury in HUA. In contrast, an increased abundance of Bacteroides was associated with improved inflammatory status in HUA mice. In conclusion, CSF may ameliorate hyperuricemia by modulating immune inflammation and gut microecological disorders, potentially through regulating gut microbiota diversity and modifying the abundances of Muribaculaceae, Prevotella, and Bacteroides.

Key words: Capparis spinosa fruit, immuno-inflammation, gut microbiota, hyperuricemia

中图分类号:  R932