Abstract：Objective: To investigate the influence and mechanism of paeoniflorin (PF) on wound healing in rats with refractory ulcer by regulating hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2). Methods: Sixty SD rats were randomly grouped into Sham operation (Sham) group, Model group, PF group (30 mg/kg,twice a day), PX-478 group (100 mg/kg HIF-1α/VEGF/VEGFR2 pathway inhibitor PX-478,once a day), and PF+PX-478 group, 12 animals in each group, twice a day, for 2 weeks. The rat model of refractory wound was made by injecting hydrocortisone into the general wound surface. The camera combined with Image J software was used to calculate the wound healing rate of each group of rats; ELISA method was used to detect oxidative stress indicators in rat serum; HE staining was used to detect the pathological changes of rat wounds; TUNEL staining was used to detect apoptosis in wound tissue; RT-qPCR was used to detect the expressions of transforming growth factor β1 (TGF-β1) and platelet-derived factor (PDGF) in rat wound tissue; Western blotting was used to detect the expression of HIF-1α/VEGF/VEGFR2 pathway-related proteins in rat wound tissue. Results: Compared with the Sham group, the wound fibroblasts and capillaries of the rats in the Model group were sparse, the healing rate, levels of SOD, GSH-PX, mRNA levels of TGF-β1, PDGF, and protein levels of HIF-1α, VEGF, VEGFR2 were obviously decreased (P<0.05), the level of MDA and the apoptosis rate of wound tissue were obviously increased (P<0.05); compared with the Model group, the wound fibroblasts and capillaries of the rats in the PF group were denser (P<0.05), the healing rate, levels of SOD, GSH-PX, mRNA levels of TGF-β1, PDGF, and protein levels of HIF-1α, VEGF, VEGFR2 were obviously increased (P<0.05), the level of MDA and the apoptosis rate of wound tissue were obviously decreased (P<0.05), the corresponding indicators in the PX-478 group showed opposite trends (P<0.05); compared with the PF group, the wound fibroblasts and capillaries of the rats in the PF+PX-478 group were sparse (P<0.05), the healing rate, levels of SOD, GSH-PX, mRNA levels of TGF-β1, PDGF, and protein levels of HIF-1α, VEGF, VEGFR2 were obviously decreased (P<0.05), and the level of MDA and the apoptosis rate of wound tissue were obviously increased (P<0.05). Conclusion: PF may improve wound healing in rats with refractory ulcer by activating the HIF-1α/VEGF/VEGFR2 pathway.
2023, Vol. 29 
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