Negative pressure wound therapy promotes wound healing by regulating riboflavin and glutathione metabolism: based on metabolomics
10.3760/cma.j.cn114453-20240816-00212
- VernacularTitle:核黄素和谷胱甘肽在负压伤口疗法促进创面愈合中的作用：基于代谢组学研究
- Author:
Xinwen KUANG
1
;
Zhengyun LIANG
;
Yijun XIA
;
Mengjie SHAN
;
Yan HAO
;
Cheng FENG
;
Zhi WANG
;
Youbin WANG
Author Information
1. 中国医学科学院北京协和医学院北京协和医院整形美容外科，北京 100032
- Publication Type:Journal Article
- Keywords:
Negative-pressure wound therapy;
Non-targeted metabolomics;
Riboflavin;
Glutathione;
Spermidine;
Redox reaction
- From:
Chinese Journal of Plastic Surgery
2025;41(10):1061-1071
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role and mechanism of negative pressure wound therapy (NPWT) in a rabbit full-thickness wound model using non-targeted metabolomics.Methods:Eighteen male New Zealand rabbits (11-12 weeks old) were used. Two symmetrical circular full-thickness skin defects were created on the back of each rabbit. The animals were randomly divided into three groups: Control group (no treatment), Saline group (debridement with saline irrigation), and NPWT+ Saline group (saline debridement followed by 2 h of NPWT at -125 mm Hg once daily for two weeks). Wound healing was documented on days 0, 3, 7, 10, and 14. The wound healing rate was calculated as (original area-unhealed area)/original area × 100%. Histopathological changes were evaluated via hematoxylin and eosin (HE) staining. Metabolomic profiling of wound tissues was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Differential metabolites were identified, and pathway enrichment analysis was conducted. Oxidative stress markers, including superoxide dismutase (SOD) and catalase (CAT) activities and malondialdehyde (MDA) content, were measured using commercial kits. Data were analyzed using SPSS 20.0. One-way ANOVA with Tukey’s HSD test or Welch’s ANOVA with Games-Howell test was applied as appropriate.Results:On days 3, 10, and 14, the wound healing rate in the NPWT+ Saline group was significantly higher than that in the Control and Saline groups ( P<0.05). On day 7, the NPWT+ Saline group showed a significantly higher healing rate than the Saline group ( P<0.01), but no significant difference compared with the Control group ( P>0.05). HE staining on day 7 revealed enhanced epithelialization, thicker granulation tissue, higher microvessel density, and more abundant, well-organized collagen in the NPWT+ Saline group. By day 14, all groups had formed relatively continuous epithelial structures. Non-targeted metabolomics identified riboflavin and spermidine as differential metabolites. Pathway analysis highlighted riboflavin metabolism and glutathione metabolism as the most significantly enriched pathways. Compared with the Control and Saline groups, the NPWT+ Saline group exhibited significantly increased CAT and SOD activities ( P<0.05) and decreased MDA content ( P<0.01), indicating reduced oxidative stress. Conclusion:NPWT may promote wound healing by elevating riboflavin and spermidine levels, thereby modulating riboflavin and glutathione metabolism and regulating local redox reactions.
