[Research progress on the role of calcitonin gene-related peptide in the repair of diabetic wounds].

内容摘要

Diabetic wounds are a severe complication of diabetes, which can lead to amputation or even mortality in severe cases. While normal wound healing consists of four phases: hemostasis, inflammation, proliferation, and remodeling, diabetic wounds tend to become chronic and refractory primarily due to a prolonged inflammatory phase. In diabetic wounds, insufficient synthesis and release of endogenous calcitonin gene-related peptide (CGRP) is a critical upstream mechanism underlying the disrupted neuro-immune communication, the persistent inflammation, and the arrested wound healing process. In contrast to pure skin defect wounds, where CGRP is rapidly upregulated after injury, CGRP remains persistently low in diabetic wound tissue, consequently failing to drive macrophage polarization towards the M2 phenotype or promote vascular maturation and collagen fiber deposition in the later phase of inflammation. In the early inflammatory phase, CGRP exerts pro-inflammatory effects by enhancing angiogenesis and modulating macrophage polarization. In the late inflammatory phase, CGRP upregulates thrombospondin-1, promotes neutrophil apoptosis and phagocytic clearance, thereby inhibiting excessive inflammatory response and shifting the wound microenvironment from a pro-inflammatory state to a pro-reparative state. Restoring CGRP signaling reconstructs the neuroimmunomodulation axis and improves wound repair while relieving diabetic neuropathic pain. Engineered CGRP combined with intelligent delivery systems offers promising prospects for diabetic wound therapy. However, large-scale clinical trials are still required to validate its clinical efficacy and safety. This paper systematically analyzes the mechanisms and application strategies of CGRP in facilitating diabetic wound repair, which can provide a theoretical basis and innovative strategies for clinical management. 糖尿病创面是一种糖尿病并发症，严重者可致患者截肢甚至死亡。正常的创面愈合历经止血、炎症、增殖、重塑4个阶段，糖尿病创面主要因炎症期延长而慢性难愈。糖尿病创面组织中降钙素基因相关肽（CGRP）合成与释放不足，这是导致创面神经免疫通讯中断、炎症无法消退、愈合进程停滞的关键上游机制。与单纯皮肤缺损创面中CGRP在伤后迅速上调不同，糖尿病创面组织中CGRP呈持续性低水平表达，无法在炎症后期驱动巨噬细胞向M2型极化，促进血管成熟与胶原纤维沉积。在炎症初期，CGRP通过促进新血管生成、调节巨噬细胞极化等发挥促炎作用；而在炎症后期，CGRP通过上调血小板反应蛋白-1，促进中性粒细胞凋亡与胞葬清除，进而抑制过度炎症反应，推动创面微环境由促炎状态向促修复状态转变。恢复CGRP信号可重塑神经免疫调控轴，兼具促进创面修复与缓解糖尿病神经病理性疼痛的双重作用。工程化CGRP与智能递送系统为糖尿病创面治疗带来新希望，但其在临床应用中的有效性与安全性仍需大规模研究验证。该文深入剖析CGRP在糖尿病创面修复中的作用机制及应用策略，为临床治疗提供理论依据与新思路。.