Exogenous hydrogen sulphide supplement accelerates skin wound healing via oxidative stress inhibition and vascular endothelial growth factor enhancement

Abstract

Hydrogen sulphide (H₂ S) is an important gasotransmitter with several physiological functions. However, the roles and the detailed mechanisms of H₂ S on skin wound healing are not known well. In the present study, 129S1/SvImJ mice were intraperitoneally injected with NaHS (50 μmol/kg/d) for 2 weeks. Then, a round wound of 6 mm diameter with depth into the dermis was made. The skin wound area, blood perfusion, superoxide production, malondialdehyde (MDA) levels, total antioxidant capacity (T-AOC), expression of vascular endothelial growth factor (VEGF), dynamin-related protein 1 (DRP1) and optic atrophy 1 (OPA1) were measured. After NaHS (50 μmol/L) pre-administration for 4 hours, cell migration rate, DRP1, OPA1 and α-smooth muscle actin (α-SMA) expression, superoxide production and mitochondrial membrane potential in primary skin fibroblasts were measured. Tube formation in human umbilical vein endothelial cells (HUVECs) and cell migration in human keratinocytes were also measured. The results showed that NaHS pretreatment significantly accelerated wound healing and improved blood flow in the wound after operation. NaHS increased VEGF expression in the wound and promoted tube formation in HUVECs. Meanwhile, NaHS attenuated reactive oxygen species (ROS) production, suppressed MDA level but restored T-AOC in the wound. NaHS also promoted skin fibroblasts migration and α-SMA expression after scratch. Moreover, NaHS alleviated ROS, increased mitochondrial membrane potential, decreased DRP1 but enhanced OPA1 expression in skin fibroblasts after scratch. NaHS also accelerated human keratinocytes migration after scratch. Taken together, exogenous H₂ S supplementary accelerated the skin wound healing, which might be related to oxidative stress inhibition and VEGF enhancement.

Keywords: hydrogen sulphide; reactive oxygen species; skin fibroblasts; vascular endothelial growth factor; wound healing.