Hydrogen sulfide improves diabetic wound healing in ob/ob mice via attenuating inflammation

The proposed mechanisms of impaired wound healing in diabetes involve sustained inflammation, excess oxidative stress and compromised agiogenesis. Hydrogen sulfide (H₂S) has been reported to have multiple biological activities. We aim to investigate the role of H₂S in impaired wound healing in ob/ob mice and explore the possible mechanisms involved.

Full-thickness skin dorsal wounds were created on ob/ob mice and C57BL/6 mice. Cystathionine-γ-lyase (CSE) expression and H₂S production were determined in granulation tissues of the wounds. Effects of NaHS on wound healing were evaluated. Inflammation and angiogenesis in granulation tissues of the wounds were examined.

CSE expression, and H₂S content were significantly reduced in granulation tissues of wounds in ob/ob mice compared with control mice. NaHS treatment significantly improved wound healing in ob/ob mice, which was associated with reduced neutrophil and macrophage infiltration, decreased production of tumor necrosis factor (TNF)-α, interleukin (IL)-6. NaHS treatment decreased metalloproteinase (MMP)-9, whereas increased collagen deposition and vascular-like structures in granulation tissues of wounds in ob/ob mice.

CSE down-regulation may play a role in the pathogenesis of diabetic impaired wound healing. Exogenous H₂S could be a potential agent to improve diabetic impaired wound healing by attenuating inflammation and increasing angiogenesis.