孙 娟,牛旭东

目的：基于公共转录组数据描述糖尿病足溃疡（DFU）的氧化应激、炎症和组织修复相关表达特征，并探索硅基生物活性材料的潜在作用靶点。方法：获取GEO数据集GSE80178中6例DFU组织及6例足部皮肤对照（3例糖尿病非溃疡足、3例非糖尿病足）的作者处理数据。按FDR<0.05且|log2FC|>1筛选差异表达条目，围绕Nrf2/NF-κB、炎症因子、巨噬细胞标志物、细胞外基质、表皮分化及血管内皮相关基因开展预设靶向分析。结果：共获得4085个差异表达条目，其中991个上调、3094个下调。NFE2L2下调，而HMOX1、TXN及PTGS2上调；IL1A、IL1B和CCL20升高。CD68升高，CD163、MRC1和ARG1降低；同时MMP1显著升高，COL1A2、ACTA2、CDH5、VWF和TEK降低。结论：DFU组织呈现抗氧化调控异常、持续炎症以及基质与血管修复受损并存的转录特征。该结果支持将Nrf2/NF-κB-IL-1/MMP轴作为硅基材料的候选验证方向，但不能据此证明细胞极化状态、通路活性或材料疗效，仍需独立队列和实验验证。

糖尿病足溃疡；转录组；氧化应激；免疫微环境；硅基生物活性材料

[1] Armstrong DG,Boulton AJM,Bus SA.Diabetic foot ulcers and their recurrence.N Engl J Med.2017;376(24):2367-2375. [2] Schaper NC,van Netten JJ,Apelqvist J,et al.Practical guidelines on the prevention and management of diabetes-related foot disease (IWGDF 2023 update).Diabetes Metab Res Rev.2024;40(3):e3657. [3] Kunkemoeller B,Kyriakides TR.Redox signaling in diabetic wound healing regulates extracellular matrix deposition.Antioxid Redox Signal.2017;27(12):823-838. [4] Ramirez HA,Pastar I,Jozic I,et al.Genomic profiling of diabetic foot ulcers identifies miR-15b-5p as a major regulator that leads to suboptimal inflammatory response and diminished DNA repair mechanisms.J Invest Dermatol.2018;138(2):364-374. [5] Mehrabi T,Mesgar AS,Mohammadi Z.Bioactive glasses:a promising therapeutic ion release strategy for enhancing wound healing.ACS Biomater Sci Eng.2020;6(10):5399-5430. [6] Xu J,Lin Y,Wang Y,et al.Multifunctional regeneration silicon-loaded chitosan hydrogels for MRSA-infected diabetic wound healing. Adv Healthc Mater.2024;13(10):e2303501. [7] Morgan MJ,Liu ZG.Crosstalk of reactive oxygen species and NF-κB signaling.Cell Res.2011;21(1):103-115. [8] Wardyn JD,Ponsford AH,Sanderson CM.Dissecting molecular cross-talk between Nrf2 and NF-κB response pathways.Biochem Soc Trans.2015;43(4):621-626. [9] Wynn TA,Vannella KM.Macrophages in tissue repair,regeneration,and fibrosis.Immunity.2016;44(3):450-462. [10] Lin CW,Hung CM,Chen WJ,et al.New horizons of macrophage immunomodulation in the healing of diabetic foot ulcers. Pharmaceutics.2022;14(10):2065. [11] Li M,Yu H,Pan H,et al.Nrf2 suppression delays diabetic wound healing through sustained oxidative stress and inflammation.Front Pharmacol.2019;10:1099.

点击下载PDF