医学分子生物学杂志 ›› 2026, Vol. 23 ›› Issue (5): 531-540.doi: 10.3870/j.issn.1672-8009.2026.05.007

• 论著 • 上一篇    下一篇

白藜芦醇通过SRC/FGFR1轴改善糖尿病足的分子机制研究

谷雯雯, 谢娟   

  1. 安徽医科大学第二附属医院整形与创面修复外科 合肥市, 230000
  • 收稿日期:2025-10-17 出版日期:2026-09-30 发布日期:2026-09-30
  • 通讯作者: 谢娟(E-mail:xiejuan0621@163.com)
  • 基金资助:
    安徽省卫生健康科研项目(No.AHWJ2023A20229).

Resveratrol Ameliorates Diabetic Foot via the SRC/FGFR1 Axis

GU Wenwen, XIE Juan   

  1. Department of Plastic and Wound-Repair Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230000, China
  • Received:2025-10-17 Online:2026-09-30 Published:2026-09-30
  • Contact: XIE Juan(E-mail:xiejuan0621@163.com)
  • Supported by:
    Anhui Provincial Health Research Project(No.AHWJ2023A20229)

摘要: 目的 探讨白藜芦醇(resveratrol,RES)通过非受体酪氨酸激酶肉瘤病毒蛋白(SRC proto-oncogene, non-receptor tyrosine kinase,SRC)/成纤维细胞生长因子受体1(fibroblast growth factor receptor 1,FGFR1)轴影响糖尿病足进展的分子机制。方法 将人皮肤成纤维细胞(human dermal fibroblasts,HDF)分为正常葡萄糖(NG)组、高葡萄糖(HG)组、HG+RES组。CCK-8检测细胞增殖活力,Transwell检测细胞迁移,TUNEL检测细胞凋亡。生物信息分析RES治疗糖尿病足的可能靶点并探究其中涉及的信号通路。进一步将HDF细胞分为NG组、HG组、HG+si-SRC组、HG+oe-SRC组、HG+oe-SRC+si-FGFR1组,测定SRC与FGFR1表达变化对细胞增殖活力、迁移能力与凋亡的影响。构建糖尿病足动物模型,RES干预治疗,α硫辛酸作为阳性对照,分析RES对于糖尿病足动物模型的治疗潜力。结果 生物信息学分析发现SRC作为RES与糖尿病足分子靶点交集之一,也是内分泌抵抗途径的关键分子。与NG组相比,HG组HFD细胞SRC表达增强,细胞增殖活力与迁移能力降低、凋亡增加;而RES干预能够逆转这一结果(P<0.05)。相比于HG组,敲减HDF细胞中的SRC,细胞活力与迁移能力提升,凋亡减少;而过表达SRC进一步抑制细胞增殖活力与迁移能力,并促进细胞凋亡,联合敲减FGFR1则能部分逆转这一结果(P<0.05)。动物实验证实RES与α硫辛酸能够对糖尿病足发挥治疗作用。结论 RES通过抑制SRC/FGFR1轴促进糖尿病足改善。

关键词: 白藜芦醇, 非受体酪氨酸激酶肉瘤病毒蛋白, 成纤维细胞生长因子受体1, 糖尿病足

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

中图分类号: