血管生成与脂肪组织代谢重塑在糖尿病足溃疡愈合中的作用及治疗潜力
Angiogenesis and Adipose Tissue Metabolic Remodeling in the Healing of Diabetic Foot Ulcers and Their Therapeutic Potential
尚俊良 1徐旭英1
作者信息
- 1. 100010 北京市，首都医科大学附属北京中医医院
- 折叠
摘要
糖尿病足溃疡（DFU）是糖尿病严重且具破坏性的慢性并发症之一，给全球医疗卫生体系造成了沉重负担。DFU难以愈合的根本原因在于其并非单纯的局部病变，而是全身性代谢紊乱在局部的体现。本文系统阐述了血管生成障碍与脂肪组织代谢重塑这两个核心病理环节在DFU愈合性中的关键作用及二者间的相互关联。在糖尿病状态下，高糖毒性、晚期糖基化终末产物蓄积和生长因子信号失调共同阻碍局部血管生成，具体表现为内皮祖细胞功能障碍、促/抗血管生成因子失衡及细胞外基质代谢紊乱。与此同时，脂肪组织发生病理性重塑，表现为脂肪细胞肥大、慢性炎症及脂肪因子谱失调，并通过释放促炎因子与游离脂肪酸，构建起系统性促炎微环境。这两种机制并非孤立存在，而是通过“脂肪-血管轴”相互交织：脂肪组织炎症会加剧内皮功能障碍与血管生成失败，而局部血供不足又进一步恶化脂肪组织缺氧及功能紊乱，形成恶性循环，最终导致伤口持续炎症、修复细胞能量危机及愈合停滞。基于上述机制，本文综述了针对这一恶性循环的多模式治疗策略，包括从源头改善脂肪组织功能的系统性干预，以及局部促进血管再生的方法。未来，通过整合系统性代谢调控与局部再生医学的多靶点、个体化联合治疗方案，有望突破现有瓶颈，为DFU的治愈提供新的路径。
Abstract
Diabetic foot ulcer (DFU) represents one of the most severe and devastating chronic complications of diabetes mellitus, imposing a substantial burden on health care systems worldwide. The refractory nature of DFU stems from its characterization not merely as a localized lesion, but as a local manifestation of systemic metabolic dysregulation. This review systematically examines the pivotal roles of impaired angiogenesis and adipose tissue metabolic remodelingtwo interrelated core pathologic processesin the nonhealing phenotype of DFU and explores their intricate interdependence.In the diabetic state, hyperglycemia-induced toxicity, accumulation of advanced glycation end products, and dysregulation of growth factor signaling cascades collectively impair local neovascularization. These abnormalities manifest as endothelial progenitor cell dysfunction, an imbalance between proangiogenic and antiangiogenic factors, and extracellular matrix remodeling dyshomeostasis. Concurrently, adipose tissue undergoes pathologic remodeling characterized by adipocyte hypertrophy, chronic low-grade inflammation, and an altered adipokine secretory profile, thereby establishing a systemic proinflammatory milieu through the release of inflammatory mediators and free fatty acids.These two pathogenic mechanisms do not operate independently but are intimately linked through an "adipose-vascular axis." Adipose tissue inflammation exacerbates endothelial dysfunction and impairs angiogenesis, while compromised local perfusion further aggravates adipose tissue hypoxia and functional derangement, thereby perpetuating a vicious cycle. This interconnected pathology ultimately culminates in persistent wound inflammation, impaired cellular energy metabolism in reparative cells, and arrested healing progression.Based on these mechanistic insights, this review evaluates multimodal therapeutic strategies targeting this pathogenic cycle, including systemic interventions that ameliorate adipose tissue dysfunction at its source and localized approaches that promote vascular regeneration. Future directions should focus on integrating systemic metabolic modulation with regional regenerative medicine through multi-targeted, personalized combination regimens, potentially overcoming current therapeutic limitations and offering novel pathways for DFU healing.关键词
糖尿病足/溃疡/血管生成/脂肪组织/脂肪因子/胰岛素抵抗/脂肪源性干细胞/外泌体/治疗策略引用本文复制引用
尚俊良,徐旭英.血管生成与脂肪组织代谢重塑在糖尿病足溃疡愈合中的作用及治疗潜力[EB/OL].(2026-03-19)[2026-03-22].https://chinaxiv.org/abs/202603.00108.学科分类
医学研究方法/临床医学
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