Hydrogen-Rich Saline Accelerates Diabetic Wound Healing in Vivo and Its Interaction with the Renin-Angiotensin System Pathway
Genwang Wang, Qiong Wu, Yasong Yang, Nan Hong, Shuqiang Chen, Jie Li, Pan YuAim:
Oxidative stress and chronic inflammation represent two major contributors to slowing the process of diabetic wound healing. So far, there is a lack of characterization of the mechanistic role of hydrogen-rich saline (HRS), despite its antioxidant potential, in diabetic wound repair. This study was conducted to investigate the therapeutic effects of hydrogen-rich saline on wound healing in a diabetic mouse model and to elucidate the underlying mechanisms.
Materials and methods:
Full-thickness skin wounds were created in diabetic mice to assess wound closure on days 0, 4, 7, 10, and 14. Hematoxylin-eosin staining and Masson staining were employed to evaluate the histopathology, while transmission electron microscopy was used to examine the fibroblast ultrastructure. Furthermore, immunohistochemistry and western blot were adopted to detect the expression of nuclear factor kappa-B (NF-κB), transforming growth factor-- beta (TGF-β), and proliferating cell nuclear antigen (PCNA). Additionally, HRS-regulated proteins were identified by proteomic sequencing, with key targets validated by western blot.
Results:
HRS significantly accelerated diabetic wound healing by lowering the levels of O2•− and malondialdehyde (MDA) in wound tissues and inhibiting the expression of NF-κB. HRS increased the levels of TGF-β and PCNA. Proteomics indicated that the therapeutic effect of HRS was associated with the renin-angiotensin system (RAS) pathway, as validated by western blot validation of key RAS components.
Discussion:
HRS is a promising therapeutic strategy for chronic diabetic wounds. However, the observed association between HRS and the RAS pathway is correlative; functional experiments (e.g., RAS inhibition or gene knockdown) are needed to establish causality. Overall, this study provides a new mechanistic perspective on HRS therapy in diabetic wounds.
Conclusions:
This study confirmed that HRS promotes diabetic wound healing by alleviating oxidative stress and inflammation, and these effects may be mechanistically associated with the RAS pathway.