Roxadustat promotes hypoxia‐inducible factor‐1α/vascular endothelial growth factor signalling to enhance random skin flap survival in rats

Abstract

Random skin flaps have limited clinical application as a broad surgical reconstruction treatment because of distal necrosis. The prolyl hydroxylase domain‐containing protein inhibitor roxadustat (RXD) enhances angiogenesis and reduces oxidative stress and inflammation. This study explored the function of RXD in the survival of random skin flaps. Thirty‐six male Sprague–Dawley rats were randomly divided into low‐dose RXD group (L‐RXD group, 10 mg/kg/2 day), high‐dose RXD group (H‐RXD group, 25 mg/kg/2 day), and control group (1 mL of solvent, 1:9 DMSO:corn oil). The proportion of surviving flaps was determined on day 7 after surgery. Angiogenesis was assessed by lead oxide/gelatin angiography, and microcirculation blood perfusion was evaluated by laser Doppler flow imaging. Specimens in zone II were obtained, and the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) were measured as indicators of oxidative stress. Histopathological status was evaluated with haematoxylin and eosin staining. The levels of hypoxia‐inducible factor‐1α (HIF‐1α), vascular endothelial growth factor (VEGF), and the inflammatory factors interleukin (IL)‐1β, IL‐6, and tumour necrosis factor‐α (TNF‐α) were detected by immunohistochemistry. RXD promoted flap survival and microcirculatory blood perfusion. Angiogenesis was detected distinctly in the experimental group. SOD activity increased and the MDA level decreased in the experimental group. Immunohistochemistry indicated that the expression levels of HIF‐1α and VEGF were increased while the levels of IL‐6, IL‐1β, and TNF‐α were decreased after RXD injection. RXD promoted random flap survival by reinforcing vascular hyperplasia and decreasing inflammation and ischaemia‐reperfusion injury.

Enhancing wound healing and overcoming cisplatin resistance in ovarian cancer

“…On fibroblast cultures, wound repair assay was conducted subsequent to transfection. To determine the rate of wound closure, a cut was made in the cell monolayer and the migration of fibroblasts into the wound area will be quantified and monitored 24–26 …”

“…To determine the rate of wound closure, a cut was made in the cell monolayer and the migration of fibroblasts into the wound area will be quantified and monitored. 24 , 25 , 26 …”

“…Important cellular processes, including fibroblast activation, pain regulation and collagen deposition, can be disrupted by dysregulated autophagy, resulting in compromised wound healing. Gaining a comprehensive understanding of the complex interplay between autophagy and wound healing yields significant knowledge for the development of therapeutic approaches that promote improved tissue regeneration and repair, particularly in pathological states characterized by autophagy disruption 26 …”

“…Gaining a comprehensive understanding of the complex interplay between autophagy and wound healing yields significant knowledge for the development of therapeutic approaches that promote improved tissue regeneration and repair, particularly in pathological states characterized by autophagy disruption. 26 …”