南方医科大学学报

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (9): 2113-2122.doi: 10.12122/j.issn.1673-4254.2026.09.11

• • 上一篇    

芪黄健脾滋肾颗粒通过调控巨噬细胞免疫代谢重编程改善系统性红斑狼疮患者的肾脏损伤

钱爱1(), 黄传兵1,2(), 朱雅文1, 胡可心1, 宋昕冉1, 许宇翔1   

  1. 1.安徽中医药大学第一附属医院，安徽 合肥 230031
    2.新安医学教育部重点实验室，安徽 合肥 230038
  • 收稿日期:2026-02-02 出版日期:2026-09-20 发布日期:2026-09-30
  • 通讯作者: 黄传兵 E-mail:1838929252@qq.com;chuanbinh@163.com
  • 作者简介:钱 爱，在读博士研究生，E-mail: 1838929252@qq.com
  • 基金资助:
    国家自然科学基金(82574970);国家中医药管理局-重大疑难疾病中西医临床协作项目(ZDYN-2024-A-146);安徽省中医优势专科(皖中医药服务秘[2022]34号);安徽省临床医学研究转化专项项目(202304295107020114);大健康研究院新安医学与中医药现代化研究所专项(2023CXMMTCM004)

Qihuang Jianpi Zishen Granule ameliorates renal injury in patients with systemic lupus erythematosus by regulating immunometabolic reprogramming of macrophages

Ai QIAN1(), Chuanbing HUANG1,2(), Yawen ZHU1, Kexin HU1, Xinran SONG1, Yuxiang XU1   

  1. 1.First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China
    2.Ministry of Education Key Laboratory of Xin'an Medicine, Hefei 230038, China
  • Received:2026-02-02 Online:2026-09-20 Published:2026-09-30
  • Contact: Chuanbing HUANG E-mail:1838929252@qq.com;chuanbinh@163.com
  • Supported by:
    National Natural Science Foundation of China(82574970)

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摘要：

目的 基于网络药理学、分子对接技术，通过临床验证，探讨芪黄健脾滋肾颗粒（QJZG）对系统性红斑狼疮（SLE）肾损害患者巨噬细胞极化的影响。 方法 运用TCMSP、GeneCards、DrugBank、OMIM、TTD数据库获取QJZG及SLE、肾损害相关靶点；取三者交集得到潜在作用靶点；使用Cytoscape软件版本3.10.3，构建活性化合物与潜在靶标之间的相互作用网络及蛋白质互作关系网络。基于网络拓扑分析筛选出核心化合物成分与关键靶点，进而开展分子对接模拟验证。临床纳入62例SLE患者和30例健康人，将SLE患者分为观察组和对照组（n=31）；运用Western blotting技术检测巨噬细胞极化相关蛋白（iNOS、Arg-1）的表达，RT-qPCR技术检测AMPK/ULK1信号通路（AMPK、mTOR、HIF-1α、ULK1）mRNA表达；并观察经QJZG干预后对SLE患者中医证候积分、肾功能（CREA、BUN、eGFR）及免疫功能指标（CD4+T cell、CD8+T cell、CD4+T cell/CD8+T cell）表达的影响。 结果 经筛选得到QJZG作用于SLE肾损害的关键活性成分3种，核心靶点基因9个；富集分析显示可能涉及TNF、HIF-1、mTOR、cAMP等信号通路；分子对接模拟分析表明，所选核心活性成分与潜在关键靶点之间展现出良好的结合能力，呈现出类似的结合活性特征，其中HIF-1α、mTOR是结合活性较好的靶蛋白。临床试验证实QJZG能够显著降低血清中CREA、BUN、iNOS蛋白、mTOR mRNA、HIF-1α mRNA、CD8+T cell表达水平（P<0.01），升高血清中eGFR、Arg-1蛋白、AMPK mRNA、ULK1 mRNA、CD4+T cell、CD4+T cell/CD8+T cell水平（P<0.01），降低中医证候积分（P<0.01）。 结论 揭示了QJZG通过多成分、多靶点协同调控SLE肾损伤的作用特征。复方中所含的槲皮素、山奈酚及7-O-甲基异微凸剑叶莎醇等代表性组份，可能通过与HIF-1α、mTOR等靶点结合，激活AMPK/ULK1信号通路，进而调控巨噬细胞极化，体现了中药复方“整体调控、多途径干预”的独特优势。

关键词: 芪黄健脾滋肾颗粒, 系统性红斑狼疮, 巨噬细胞M1/M2极化, AMPK/ULK1信号通路, 网络药理学

Abstract:

Objective To investigate the mechanism of Qihuang Jianpi Zishen Granule (QJZG) for regulating macrophage polarization in renal damage in patients with systemic lupus erythematosus (SLE). Methods Public databases were used to screen the targets of QJZG, SLE and renal damage. An active ingredient-target network and a protein-protein interaction network were constructed followed by molecular docking. Sixty-two SLE patients were randomized into QJZG treatment group and control group (n=31), with 30 healthy individuals as the normal control group. Macrophage polarization markers (iNOS and Arg-1) and AMPK/ULK1 pathway molecules were detected using Western blotting and RT-qPCR, and the changes in renal function, immune indicators, and TCM syndrome scores of the participants were evaluated. Results Three key active ingredients of QJZG (quercetin, kaempferol, and 7-O-methylisoflavanone) and 9 core targets were identified, and the target genes were enriched in the TNF, HIF-1, and mTOR pathways. Molecular docking showed strong binding of the active compounds of QJZG with HIF-1α and mTOR. In SLE patients, QJZG treatment significantly improved their renal function, regulated the immune function (increasing CD4+/CD8+ ratio and reducing CD8+ T cells), and reduced TCM syndrome scores. QJZG treatment also significantly downregulated iNOS, mTOR, and HIF-1α expressions and upregulated Arg-1, AMPK, and ULK1 expression in SLE patients. Conclusion QJZG alleviated renal damage in SLE patients through a mechanism involving multiple components and targets. The active ingredients of QJZG regulate macrophage polarization possibly by activating the AMPK/ULK1 pathway via binding to their targets including HIF-1α and mTOR.

Key words: Qihuang Jianpi Zishen Granules, systemic lupus erythematosus, M1/M2 polarization of macrophages, AMPK/ULK1 signaling pathway, network pharmacology