巨噬细胞-淋巴管轴在慢性难愈合创面中的作用及干预研究进展

Research progress on the role and intervention of the macrophage-lymphatic vessel axis in chronic non-healing wounds

摘要

慢性难愈合创面，如糖尿病足溃疡、静脉性溃疡和烧伤创面，是临床中常见的修复难题，愈合迟缓且并发症风险高。研究发现，巨噬细胞通过表型转换调控淋巴管生成及功能，形成“巨噬细胞-淋巴管轴”，在创面修复中发挥关键作用。该轴以白细胞介素 4（IL-4）/信号转导及转录激活因子 6（STAT6）-血管内皮生长因子 C（VEGF-C）/血管内皮生长因子受体 3（VEGFR-3）-磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）信号通路为核心，通过旁分泌、外泌体以及细胞间接触等方式影响淋巴内皮细胞增殖、迁移和管腔形成。尽管不同病因导致的创面类型各异，糖尿病创面、静脉性溃疡及烧伤创面均表现出巨噬细胞修复性转换受阻、淋巴管生成不足和功能障碍等共性特征。西医靶向治疗、中药活性成分及中西医结合干预通过多环节调控打破炎症持续和修复停滞的循环。文章综述了巨噬细胞-淋巴管轴在慢性创面中的作用机制、失调特点及干预方法。

Abstract

Chronic non-healing wounds, such as diabetic foot ulcers, venous ulcers, and burn wounds, represent a persistent clinical challenge due to delayed repair and high risk of complications. Studies have shown the role of macrophages in regulating lymphatic vessel formation and function through phenotypic transitions, forming what is referred to as the “macrophage–lymphatic axis”. This axis relies on IL-4/STAT6-VEGF-C/VEGFR-3-PI3K/Akt signaling, and coordinates lymphatic endothelial cell proliferation, migration, and lumen formation via paracrine signals, exosomes, and direct cell interactions. Despite differences in etiology, these chronic wounds share common features, including insufficient macrophage reparative polarization, impaired lymphangiogenesis, and compromised lymphatic drainage. Targeted Western medicine therapies, bioactive components of traditional Chinese medicine (TCM), and integrated TCM-Western medicine interventions can break the cycle of persistent inflammation and stalled repair by modulating multiple steps in these processes. This review summarizes current understanding of the macrophage-lymphatic axis in chronic wound repair, its dysregulation, and potential interventions.

关键词

巨噬细胞-淋巴管轴 / 巨噬细胞极化 / 淋巴管新生 / 慢性难愈合创面 / 中西医结合干预

Key words

Macrophage-lymphatic axis / Macrophage polarization / Lymphangiogenesis / Chronic non-healing wounds / Integrated TCM-Western medicine interventions

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基金资助

全国名老中医药专家传承工作室建设项目(国中医药人教函[2022]75号)

南京市卫生科技发展专项资金项目(YKK24203)

江苏卫生健康职业学院校级科研项目(JKCY202401)