摘要目的:探讨长链非编码RNA生长停滞特异性转录因子5（LncRNA GAS5）及微小RNA-205（miR-205）在糖尿病足溃疡（DFU）组织中的表达特征及其临床相关性，并初步揭示其在DFU中的潜在发病机制。方法:该研究为前瞻性队列研究。收集2021年2月至2023年6月于新疆医科大学第一附属医院就诊的43例2型DFU患者（DFU组）及同期收治的33例非糖尿病下肢溃疡患者［非糖尿病足溃疡（NDFU）组］的临床资料。所有患者获得血清样本；其中DFU组21例，NDFU组19例获得足部清创组织样本。组织样本用荧光定量聚合酶链式反应技术检测LncRNA GAS5与miR-205的表达差异；血清样本通过酶联免疫吸附测定检测血清血管内皮生长因子A、白细胞介素-6及C反应蛋白水平。结合临床资料分析GAS5及miR-205表达与Wagner分级的关系。整合基因表达综合数据库（DFU皮肤组织样本10例，正常皮肤组织样本11例）验证 GAS5表达，运用R语言多维度生信分析［基因本体论/京都基因与基因组百科全书（KEGG）/基因集富集分析（GSEA）］探究其潜在调控网络。结果:40例组织样本获得患者中，DFU组LncRNA GAS5表达量低于NDFU组（0.66 AU比1.63 AU， U=297.000， P=0.005），miR-205表达量（1.41 AU比0.61 AU， U=98.000， P=0.008）水平高于NDFU组，差异均有统计学意义。76例血清样本获得患者中，DFU组血管内皮生长因子A（340.12 pg/ml比121.38 pg/ml， U=157.000， P=0.001）、白细胞介素-6［（72.92±32.45）pg/ml比（34.25±21.01）pg/ml， t=5.950， P=0.001］及C反应蛋白（3 060.95 pg/ml比 1 614.82 pg/ml， U=282.000， P=0.001）水平均高于NDFU组，差异均有统计学意义。GAS5（ P=0.129）及miR-205（ P=0.950）水平在不同Wagner分级患者中差异均无统计学意义。代谢-氧化应激失衡：GSEA提示GAS5低表达驱动氧化磷酸化［标准化富集得分（NES）=1.64］、有氧糖酵解（NES=1.57）及活性氧通路（NES=1.71）异常激活，伴随DNA损伤修复（NES=1.66）与G2/M检查点富集（NES=1.47）。炎症-修复障碍：KEGG分析提示肿瘤坏死因子-p53通路激活与过氧化物酶体增殖物激活受体γ-脂肪酸代谢抑制共存，这可能是导致DFU脂质修复缺陷的原因，与实验结果一致；血清血管内皮生长因子A升高驱动病理性血管生成，而过氧化物酶体增殖物激活受体γ激动剂通路处理的巨噬细胞差异表达（NES=1.69）与γ-干扰素/肿瘤坏死因子处理的巨噬细胞（NES=1.71）加剧局部炎症，影响上皮细胞再生。 结论:LncRNA GAS5下调/miR-205上调可能通过“代谢异常-氧化损伤-炎症修复”等机制影响DFU进展，其表达特征可能作为Wagner分级的生物标志物。

abstractsObjective:To investigate the expression characteristics and clinical significance of long non-coding RNA growth arrest-specific transcript 5 (LncRNA GAS5) and microRNA-205 (miR-205) in diabetic foot ulcer (DFU) tissues, and to preliminarily explore their potential roles in DFU pathogenesis.Methods:This study was a prospective cohort study. Clinical data were collected from 43 patients with type 2 DFU (DFU group) and 33 patients with non-diabetic lower extremity ulcers [non-diabetic foot ulcer (NDFU) group] admitted to the First Affiliated Hospital of Xinjiang Medical University between February 2021 and June 2023. Serum samples were obtained from all patients; among them, foot debridement tissue samples were collected from 21 patients in the DFU group and 19 patients in the NDFU group. The expression levels of LncRNA GAS5 and miR-205 in tissue samples were detected using quantitative real-time polymerase chain reaction. Serum levels of vascular endothelial growth factor A, interleukin-6, and C-reactive protein were measured by enzyme-linked immunosorbent assay. The relationship between GAS5 and miR-205 expression and Wagner classification was analyzed in conjunction with clinical data. The Gene Expression Omnibus database (10 DFU skin tissue samples and 11 normal skin tissue samples) was used to validate GAS5 expression. The R language-based multi-dimensional bioinformatics analysis [gene ontology/Kyoto encyclopedia of genes and genomes (KEGG) /gene set enrichment analysis (GSEA)] was employed to explore its potential regulatory network.Results:Among the 40 patients with tissue samples, the expression of LncRNA GAS5 in the DFU group was lower than that in the NDFU group (0.66 AU vs. 1.63 AU, U=297.000, P=0.005), while the expression of miR-205 (1.41 AU vs. 0.61 AU, U=98.000, P=0.008) was higher in the DFU group than in the NDFU group, with statistically significant differences. Among all 76 patients, the levels of vascular endothelial growth factor A (340.12 pg/ml vs. 121.38 pg/ml, U=157.000, P=0.001], interleukin-6 [(72.92±32.45) pg/ml vs. (34.25±21.01) pg/ml, t=5.950, P=0.001], and C-reactive protein (3 060.95 pg/ml vs. 1 614.82 pg/ml, U=282.000, P=0.001) in the DFU group were all higher than those in the NDFU group, with statistically significant differences. There was no statistically significant difference in GAS5 ( P=0.129) and miR-205 ( P=0.950) levels among patients with different Wagner grades. Metabolic-oxidative stress imbalance: GSEA suggested that low expression of GAS5 drives abnormal activation of oxidative phosphorylation [normalized enrichment score (NES)=1.64], aerobic glycolysis (NES=1.57), and reactive oxygen species pathways (NES=1.71), accompanied by enrichment of DNA damage repair (NES=1.66) and G2/M checkpoint (NES=1.47). Inflammation-repair disorder: KEGG analysis indicated coexistence of tumor necrosis factor-p53 pathway activation and peroxisome proliferator-activated receptor γ-fatty acid metabolism suppression, which may be the cause of lipid repair defects in DFU, consistent with experimental results; elevated serum vascular endothelial growth factor A drives pathological angiogenesis, while differential expression in macrophages treated with peroxisome proliferator-activated receptor γ agonist pathway (NES=1.69) and macrophages treated with interferon γ/tumor necrosis factor (NES=1.71) exacerbate local inflammation and affect epithelial cells regeneration. Conclusion:Downregulation of LncRNA GAS5/upregulation of miR-205 may affect DFU progression through mechanisms such as "metabolism-oxidative damage-inflammation". Their expression characteristics may serve as biomarkers for Wagner staging.