南方医科大学学报

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (10): 2494-2508.doi: 10.12122/j.issn.1673-4254.2026.10.18

• • 上一篇    

LGALS3作为糖尿病肾病合并心力衰竭的胞葬相关生物标志物及潜在中药治疗靶点

胡敦林1(), 郭慧1, 汪晓娟1, 李煜1, 张弛1, 陈小虎1, 聂晓莉1,2()   

  1. 1.南方医科大学中西医结合医院，广东 广州 510315
    2.广东省中西医结合医院，广东 佛山 528200
  • 收稿日期:2026-03-25 出版日期:2026-10-20 发布日期:2026-10-26
  • 通讯作者: 聂晓莉 E-mail:hudunlin1218@163.com;nxl117@163.com
  • 作者简介:胡敦林，在读硕士研究生，E-mail: hudunlin1218@163.com
  • 基金资助:
    国家中医药管理局第五批全国中医临床优秀人才研修项目(国中医药人教函〔2022〕1号);国家自然科学基金(82574988);国家自然科学基金(82374340);广东省自然科学基金(2023A1515012246)

LGALS3 is an efferocytosis-related biomarker and potential traditional Chinese medicine therapeutic target for diabetic kidney disease complicated with heart failure

Dunlin HU1(), Hui GUO1, Xiaojuan WANG1, Yu LI1, Chi ZHANG1, Xiaohu CHEN1, XiaoLi NIE1,2()   

  1. 1.Southern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou 510315, China
    2.Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Foshan 528200, China
  • Received:2026-03-25 Online:2026-10-20 Published:2026-10-26
  • Contact: XiaoLi NIE E-mail:hudunlin1218@163.com;nxl117@163.com
  • Supported by:
    National Natural Science Foundation of China(82574988)

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摘要：

目的 基于“糖-心-肾”轴，采用生物信息学与网络药理学探索糖尿病肾病（DKD）合并慢性心力衰竭（CHF）的免疫-胞葬共病机制，预测“异病同治”中药干预策略。 方法 整合公共数据库的DKD与CHF的转录组数据，利用差异表达分析结合加权基因共表达网络分析（WGCNA）构建共病核心基因集。通过蛋白质互作（PPI）网络与分子复合物检测（MCODE）算法识别枢纽基因，将其与胞葬相关基因集取交集，结合外部数据集进行多重验证，进行功能富集分析。利用Coremine Medical数据库预测调控中药，分析性味归经，分子对接验证核心成分与靶点结合。收集临床血清样本，用ELISA检测核心靶点蛋白水平。 结果 共鉴定50个共病核心基因，主要富集于磷脂酰肌醇3-激酶/蛋白激酶B（PI3K-Akt）、肿瘤坏死因子（TNF）、晚期糖基化终末产物及其受体（AGE-RAGE）及氧化磷酸化等通路，提示免疫炎症、代谢重编程及胞葬功能障碍是共病的潜在核心机制。半乳糖凝集素3（LGALS3）被识别为核心枢纽基因（Hub genes），在验证集中差异表达且与胞葬功能相关。基于Hub genes预测的黄芩、黄芪、牛膝、姜黄等216味中药，药性以寒、温为主，味多苦、甘、辛，归肝、肺、脾、肾经。临床ELISA显示，DKD+CHF组血清LGALS3显著高于健康对照组、单纯DKD组和单纯CHF组（均P<0.001）。校正协变量后，共病状态仍与LGALS3独立正相关（β=51.20，P<0.001），效应量大于NT-proBNP的独立贡献。 结论 DKD合并CHF的发生发展与炎症、代谢通路异常及胞葬介导的免疫清除障碍相关。多组学分析及初步临床验证提示，LGALS3可能是连接TNF、PI3K-Akt等炎症通路与靶器官胞葬功能障碍的关键节点。预测的黄芪、黄芩、牛膝等中药体现“益气温阳、清热化瘀、泄浊解毒”治法，可能通过靶向LGALS3调节胞葬功能及免疫代谢微环境，为心肾共病防治提供新策略和思路。

关键词: 糖尿病肾病, 慢性心力衰竭, 免疫-胞葬, 网络药理学, 分子对接, 中药预测

Abstract:

Objective To explore the immune efferocytosis mechanisms of diabetic kidney disease (DKD) complicated with chronic heart failure (CHF) in light of the glucose heart kidney axis and predict the "same treatment for different diseases" strategy using traditional Chinese medicine (TCM). Methods DKD and CHF transcriptome data from public databases were integrated to construct a core gene set using differential expression and weighted gene co-expression network analysis (WGCNA). The hub genes were intersected with an efferocytosis-related gene set, validated with external datasets, and functionally enriched. The Coremine Medical database and molecular docking were used to predict the regulatory TCMs, their properties, and affinities between the active ingredients and their targets. Clinical serum samples were collected form patients with DKD, CHF, and DKD+CHF and healthy individuals for detecting galectin 3 (LGALS3) levels. Results Fifty comorbidity core genes were identified, which were enriched mainly in the PI3K Akt, TNF, AGE RAGE, and oxidative phosphorylation pathways. LGALS3 was identified as a key efferocytosis-associated hub gene with differential expression in the validation set. The prediction results included 216 TCMs predominantly exhibiting cold or warm properties with bitter, sweet or pungent flavors and liver, lung, spleen and kidney meridian tropisms. Molecular docking suggested strong binding between the key ingredients (e.g., quercetin) and LGALS3. Serum LGALS3 levels were significantly higher in patients with DKD+CHF than in those with DKD or CHF alone or healthy controls (all P<0.001). After adjusting for covariates, comorbid status remained independently and positively associated with LGALS3 (β=51.20, P<0.001), exceeding the independent contribution of NT proBNP. Conclusion DKD-CHF is associated with inflammatory/metabolic abnormalities and impairment of efferocytosis-mediated immune clearance. LGALS3 is a critical node connecting inflammatory pathways to target organ efferocytosis dysfunction. The predicted TCMs highlight the TCM therapeutic principles of "supplementing Qi, clearing the heat and resolving stasis" and may regulate efferocytosis and the immunometabolic microenvironment by targeting LGALS3.

Key words: diabetic kidney disease, chronic heart failure, immune-efferocytosis, network pharmacology, molecular docking, traditional Chinese medicine prediction