Platelet-rich plasma promotes diabetic ulcer repair through inhibition of ferroptosis

BACKGROUND: Ferroptosis, a newly discovered form of cell death, can accumulation activates lipid peroxidation and excessive oxidative stress in a high glucose environment. These phenomena suggest there may be ferroptosis pathways in the pathological processes associated with diabetic ulcer (DU). Platelet-rich plasma (PRP) promotes the healing of DU wounds, which may be achieved by the regulation of ferroptosis pathways. Hence, the present study aimed to investigate this association and uncover the potential underlying mechanisms. METHODS: Cell injury models induced by high glucose were constructed using EA.HY926 (vascular endothelial cells), HSF (fibroblasts), and rat DU models. The MDA, total ROS, total SOD content, the gene and protein expression of GPX4, SLC7A11, and ACSL4, and the expression levels of inflammatory cytokines IL-1β, IL-10, and NLRP3 was subsequently used to evaluate the important role of ferroptosis in the pathological process of DU, and elucidating the molecular mechanism of PRP in ulcer repair. RESULTS: The results show that compared with the DU control group, the healing rate of the dorsal ulcer wound in the PRP intervention group was accelerated, and the expression levels of inflammatory cytokines IL-1β, IL-10, and NLRP3 in the granulation tissue of ulcer wounds was lower. Further, the expression levels of CD31 and VEGF were higher, the gene and protein expression levels of GPX4 and SLC7A11 were increased, the expression levels of ACSL4 were less, the SOD content was higher, and the MDA content was lower. CONCLUSIONS: In this study, ferroptosis was preliminarily verified in DUs at the cellular and animal levels, while PRP could inhibit ferroptosis and significantly improve the migration and regeneration ability of fibroblasts and vascular endothelial cells induced by high glucose.