Reddi Renitha, Tan Matthew, Davies Alun Huw, Onida Sarah
Section of Vascular Surgery, Department of Surgery & Cancer, Imperial College London, Charing Cross Hospital, London, UK.
Royal College of Surgeons Ireland, Dublin, Ireland.
Int Wound J. 2025 May;22(5):e70675. doi: 10.1111/iwj.70675.
Venous leg ulcers (VLUs) are common and cause significant morbidity and poor quality of life. There is a poor understanding of the biology underlying non-healing VLUs. VLU exudates may reflect the underlying wound microenvironment. This systematic review aims to identify potentially diagnostic and/or prognostic protein biomarkers within VLU fluid/exudates reported in the literature. A systematic review was reported according to PRISMA guidelines. MEDLINE and Embase databases were searched up to 31st March 2024. Full text, primary studies in English reporting on proteins identified in VLU fluid/exudate were included. Two independent reviewers performed the abstract and full-text screen. Additional publications were identified by searching the references of included studies. 46 studies were identified, with nine comparing healing and non-healing VLUs. Cytokines (e.g., IL-1a, IL-1ra, IL-6, eotaxin, GM-CSF, PDGF, VEGF) and proteins involved in extracellular matrix (ECM) homeostasis (e.g., MMP-7, MMP-10, MMP-13, TIMP-4) were significantly increased in non-healing compared to healing VLUs. Collagen subunits (PICP and PIIINP) significantly increased as the VLU healed. Inflammatory proteins (e.g., complement type 6, S100A8, S100A9) and ECM proteins (e.g., fibronectin, lumican) were found to be increased in non-healing VLUs compared to acute surgical wounds. Altered levels of specific proteins in wound exudates may be indicative of healing and non-healing VLUs. Further work is essential to elucidate a comprehensive protein phenotype that may help early identification and prognostication of non-healing VLUs.
下肢静脉溃疡（VLUs）很常见，会导致严重的发病率和生活质量下降。人们对难愈合VLUs的生物学机制了解不足。VLU渗出液可能反映潜在的伤口微环境。本系统评价旨在确定文献中报道的VLU液体/渗出液中潜在的诊断和/或预后蛋白生物标志物。根据PRISMA指南报告了一项系统评价。检索MEDLINE和Embase数据库至2024年3月31日。纳入了以英文报道VLU液体/渗出液中鉴定出的蛋白质的全文和原始研究。两名独立评审员进行摘要和全文筛选。通过检索纳入研究的参考文献确定其他出版物。共鉴定出46项研究，其中9项比较了愈合和未愈合的VLUs。与愈合的VLUs相比，难愈合的VLUs中细胞因子（如IL-1α、IL-1ra、IL-6、嗜酸性粒细胞趋化因子、GM-CSF、PDGF、VEGF）和参与细胞外基质（ECM）稳态的蛋白质（如MMP-7、MMP-10、MMP-13、TIMP-4）显著增加。随着VLU愈合，胶原蛋白亚基（PICP和PIIINP）显著增加。与急性手术伤口相比，在难愈合的VLUs中发现炎症蛋白（如补体6型、S100A8、S100A9）和ECM蛋白（如纤连蛋白、核纤层蛋白）增加。伤口渗出液中特定蛋白质水平的改变可能表明VLUs的愈合和难愈合情况。进一步开展工作对于阐明可能有助于早期识别和预测难愈合VLUs的全面蛋白质表型至关重要。
