南方医科大学学报

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (3): 592-603.doi: 10.12122/j.issn.1673-4254.2026.03.13

• 基础研究 • 上一篇    下一篇

不同配伍黄芪药对通过PTGS2调控脂质过氧化改善小鼠糖尿病肾病

陈雪俊1(), 经媛2, 梁惠瑜1, 钟竞颖1, 陈泽栋1, 彭于芝1, 戴娇娇2(), 肖雅1()   

  1. 1.暨南大学中医学院，广东 广州 510000
    2.南方医科大学中医药学院，广东 广州 510515
  • 收稿日期:2025-09-17 出版日期:2026-03-20 发布日期:2026-03-26
  • 通讯作者: 戴娇娇,肖雅 E-mail:1962889575@qq.com;djj52092@smu.edu.cn;xiaoya0527@126.com
  • 作者简介:陈雪俊，在读硕士研究生，E-mail: 1962889575@qq.com
  • 基金资助:
    国家自然科学基金(82074307);国家自然科学基金(82574978);国家级大学生创新创业训练计划支持项目(202510559129)

Different Astragalus medicinal pairs improve diabetic nephropathy in mice by regulating lipid peroxidation through PTGS2

Xuejun CHEN1(), Yuan JING2, Huiyu LIANG1, Jingying ZHONG1, Zedong CHEN1, Yuzhi PENG1, Jiaojiao DAI2(), Ya XIAO1()   

  1. 1.School of Traditional Chinese Medicine, Jinan University, Guangzhou, 510000, China
    2.School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China
  • Received:2025-09-17 Online:2026-03-20 Published:2026-03-26
  • Contact: Jiaojiao DAI, Ya XIAO E-mail:1962889575@qq.com;djj52092@smu.edu.cn;xiaoya0527@126.com
  • Supported by:
    National Natural Science Foundation of China(82074307)

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摘要：

目的 探究芪丹地黄颗粒中不同黄芪药对（黄芪丹参药对、黄芪地黄药对、黄芪山药药对）调节糖尿病肾病（DKD）小鼠PTGS2介导的脂质过氧化的不同影响。 方法 通过网络药理学方法筛选芪丹地黄颗粒中黄芪、丹参、生地黄和山药的活性成分及其作用靶点，构建药对-有效成分-靶点网络，并与DKD相关靶点进行交集分析，构建PPI蛋白互作网络和富集分析。利用分子对接技术验证关键活性成分与PTGS2的结合能力。通过动物实验评估不同黄芪药对对DKD小鼠的影响。30只小鼠随机分为6组（n=5），包括正常对照组、模型组、厄贝沙坦组（50 mg/kg/d）及3个黄芪药对组（黄芪丹参、黄芪地黄、黄芪山药，给药剂量均为6 g/kg/d）。除正常组外，其余各组采用链脲佐菌素（50 mg/kg）诱导DKD模型，造模成功后给予相应药物干预8周。 结果 网络药理学结果显示芪丹地黄颗粒中各药对的活性成分与DKD相关靶点存在广泛交集，PTGS2为关键靶点。主要活性成分与PTGS2具有良好的结合亲和力。与模型组相比，黄芪-丹参组和黄芪-地黄组小鼠的体质量、空腹血糖、血清肌酐、尿素氮和24 h尿白蛋白水平改善（P<0.05），其中黄芪-丹参组改善最显著；而黄芪-山药组仅在血糖和肌酐水平方面有轻微改善（P<0.05），对尿素氮和尿白蛋白无统计学差异（P>0.05）。PTGS2蛋白表达在模型组升高（P<0.01），黄芪-丹参组显著下调其表达（P<0.01）。黄芪-丹参组显著提高SOD活性（P<0.01），降低MDA含量（P<0.01）并上调GPX4表达（P<0.01）；黄芪-地黄组改善作用相对较弱，黄芪-山药组效果最差。 结论 芪丹地黄颗粒中3个黄芪药对可在一定程度上通过PTGS2介导的脂质过氧化改善糖尿病肾病，其中黄芪丹参药对效果最为显著。

关键词: 芪丹地黄颗粒, 药对, 糖尿病肾病, 脂质过氧化, PTGS2

Abstract:

Objective To explore the regulatory effects of 3 Astragalus herb pairs (Astragalus-Salvia miltiorrhiza, Astragalus-Rehmannia glutinosa, and Astragalus-Dioscorea opposita) in QidanDihuang Granule on PTGS2-mediated lipid peroxidation in mice with diabetic kidney disease (DKD). Methods Network pharmacology was used to screen active components and targets of Astragalus membranaceus, Salvia miltiorrhiza, Rehmannia glutinosa, and Dioscorea opposita in Qidan Dihuang Granule to construct herb pair-active component-target networks, followed by intersection analysis with DKD-related targets for PPI network construction and enrichment analysis. Molecular docking was used to verify the binding of the key active components to PTGS2. In 25 C57BL/6J mouse models of streptozotocin-induced DKD, the therapeutic effects of treatments with saline, irbesartan, and the 3 Astragalus herb pairs (n=5) for 8 weeks were tested, with 5 normal mice serving as the control group. Results Network pharmacology showed extensive intersections between the active components of each herb pair and DKD-related targets, with PTGS2 as the key target. The major active components exhibited good binding affinity to PTGS2. The DKD mouse models in Astragalus-Salvia miltiorrhiza and Astragalus-Rehmannia glutinosa groups, particularly those in the former group, showed significant improvements in body weight, fasting blood glucose, serum creatinine, urea nitrogen, and 24-h urinary albumin. The Astragalus-Dioscorea opposita pair only slightly improved blood glucose and creatinine without improving urea nitrogen or urinary albumin in the mouse models. The Astragalus-Salvia miltiorrhiza pair, but not the other two pairs, markedly reduced the elevation of PTGS2 expression, significantly enhanced SOD activity, reduced MDA content, and upregulated GPX4 expression in the mouse models, and the therapeutic effect was only moderate in Astragalus-Rehmannia glutinosa group and the poorest in Astragalus-Dioscorea opposita group. Conclusion The 3 Astragalus herb pairs from Qidan Dihuang Granule can improve DKD in mice by reducing PTGS2-mediated lipid peroxidation, and the Astragalus-Salvia miltiorrhiza pair shows the strongest efficacy.

Key words: Qidan Dihuang Granules, herb pair, diabetic kidney disease, lipid peroxidation, PTGS2