Role of nuclear factor erythroid 2-related factor 2 in negative pressure wound therapy for diabetic foot ulcers

Abstract

BACKGROUND

Negative pressure wound therapy (NPWT) is a potential treatment for diabetic foot ulcers (DFUs), although the mechanisms underlying its effectiveness remain unclear. This study posits that NPWT may improve wound healing by promoting angiogenesis and activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like epichlorohydrin-associated protein 1 (Keap1) signaling pathway, which is crucial for the body’s defense against oxidative stress. The hypothesis indicates that enhancing antioxidant defenses through NPWT may positively affect the healing process. There are still limited data on the roles of Nrf2, its downstream signaling molecules, and angiogenesis markers in patients undergoing NPWT.

AIM

To study the mechanism of NPWT in DFUs.

METHODS

This study included a total of 40 hospitalized patients with DFUs from Xuzhou Central Hospital, who were divided into Control group (n = 21) and NPWT group (n = 19). The levels of Nrf2 and Keap1 were analyzed in the granulation tissue 7 days after treatment. The wound condition, erythrocyte sedimentation rate (ESR), procalcitonin (PCT), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), cluster of differentiation 31 (CD31), and levels of oxidative stress [malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC)] were analyzed before and 7 days after treatment by the Mann-Whitney U test.

RESULTS

The NPWT group demonstrated significant improvements in wound healing compared to the control group after 7 days of treatment. The levels of ESR, PCT, IL-6, and TNF-α were significantly reduced in the NPWT group compared to the control group (P < 0.05), while the levels of CD31, VEGF, and b-FGF showed significant increases (P < 0.05). The NPWT group exhibited notable elevations in the levels of Nrf2 and its downstream targets (SOD, CAT, and T-AOC), accompanied by decreases in the levels of Keap1 and MDA (P < 0.05).

CONCLUSION

NPWT may contribute to the healing of DFUs by potentially reducing levels of oxidative stress. Its effects could possibly be enhanced through the action of Nrf2.

Keywords: Negative pressure wound therapy; Diabetic foot ulcers; Nuclear factor erythroid 2-related factor 2; Kelch-like epichlorohydrin-associated protein 1; Healing

Core Tip: This study investigated the potential of negative pressure wound therapy (NPWT) in diabetic foot ulcers (DFUs) by assessing wound healing, inflammatory markers, cytokines, growth factors, and oxidative stress. NPWT was associated with improved wound conditions and reduced inflammation, while also increasing angiogenesis markers and antioxidant defenses that may be mediated by nuclear factor erythroid 2-related factor 2 (Nrf2). The study suggests that Nrf2 could be involved in the therapeutic effects of NPWT on DFUs.