Abstract: Objective To investigate the molecular mechanism through which resveratrol （RES） modulates the progression of diabetic foot by targeting SRC proto-oncogene, non-receptor tyrosine kinase （SRC）/fibroblast growth factor receptor 1 （FGFR1） axis. Methods Human dermal fibroblasts （HDF） were allocated into NG （normal glucose）, HG （high glucose）, and HG+RES groups. Cell proliferative viability was measured by CCK-8 assay, migration by Transwell assay, and apoptosis by TUNEL staining. Bioinformatic analyses were performed to predict potential targets of RES in diabetic foot and to explore the associated signaling pathways. HDF cells were further divided into NG, HG, HG+si-SRC, HG+oe-SRC, and HG+oe-SRC+si-FGFR1 groups to determine how alterations in SRC and FGFR1 expression affect proliferative viability, migratory capacity, and apoptosis. A diabetic foot animal model was established and treated with RES; α-lipoic acid served as the positive control to evaluate the therapeutic potential of RES. Results Bioinformatic screening identified SRC as one of the intersecting targets of RES and diabetic foot, and as a key molecule in endocrine resistance pathway. Compared with the NG group, HG-treated HDF cells exhibited up-regulated SRC expression, reduced proliferative viability and migratory capacity, and increased apoptosis; these effects were reversed by RES intervention （P<0.05）. Relative to the HG group, SRC knockdown enhanced cell viability and migration while decreasing apoptosis, whereas SRC overexpression further suppressed proliferative viability and migration and promoted apoptosis; simultaneous FGFR1 knockdown partially reversed these latter effects （P<0.05）. Animal experiments confirmed that both RES and α-lipoic acid exert therapeutic efficacy in the diabetic foot model. Conclusion Resveratrol promotes the improvement of diabetic foot by inhibiting the SRC/FGFR1 axis.

Key words: resveratrol, SRC proto-oncogene, non-receptor tyrosine kinase, fibroblast growth factor receptor 1, diabetic foot