| 王树雄,李宝成,刘毅,等.基于HIF-1α信号通路探讨高压氧治疗糖尿病大鼠足溃疡的疗效.骨科,2026,17(3): 257-262. |
| 基于HIF-1α信号通路探讨高压氧治疗糖尿病大鼠足溃疡的疗效 |
| The therapeutic effect of hyperbaric oxygen on foot ulcers in diabetic rats based on the HIF-1α signaling pathway |
| 投稿时间：2025-10-22 |
| DOI：10.3969/j.issn.1674-8573.2026.03.010 |
| 中文关键词: 缺氧诱导因子-1α 血管内皮生长因子 促红细胞生成素 高压氧治疗 糖尿病足溃疡 |
| 英文关键词: Hypoxia-inducible factor-1α Vascular endothelial growth factor Erythropoietin Hyperbaric oxygen therapy Diabetic foot ulcer |
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| 中文摘要: |
| 目的 本研究通过建立大鼠糖尿病足溃疡（diabetic foot ulcer，DFU）和下肢缺血模型，评估高压氧治疗（hyperbaric oxygen therapy，HBOT）大鼠DFU的愈合效果，并验证该疗效是否通过激活缺氧诱导因子-1α（hypoxia-inducible factor-1α，HIF-1α）信号通路及其下游血管内皮生长因子（vascular endothelial growth factor，VEGF）和促红细胞生成素（erythropoietin，EPO）实现。方法 将雄性SD大鼠18只，按随机数字表法分为3组，分别为空白对照组（正常大鼠）、糖尿病对照组（糖尿病大鼠）、高压氧实验组（糖尿病大鼠+HBOT）。糖尿病对照组和高压氧实验组建立Ⅱ型糖尿病模型后，三组均在麻醉情况下制备右下肢足背溃疡创面，且于大腿根部分离、结扎并离断股动脉，模拟缺血缺氧环境，均于术后观察5天，再将高压氧实验组行为期5天的HBOT。期间观测并记录三组大鼠双下肢温差、溃疡愈合情况，HBOT干预后溃疡处行苏木精-伊红（HE）染色检测病理变化，免疫组织化学方法分析HIF-1α、VEGF、EPO的表达情况，Western blot检测HBOT干预前后HIF-1α、VEGF、EPO蛋白相对水平变化。结果 与空白对照组和糖尿病对照组比较，高压氧实验组双下肢平均温差显著降低，溃疡恢复情况较好、面积明显缩小，且组织病理学显示纤维性修复并伴有多量的新生小血管，HIF-1α、VEGF和EPO的表达水平显著上调，表现出更优的溃疡愈合效果。高压氧实验组内HIF-1α、VEGF、EPO水平较HBOT干预前明显上调。结论 HBOT可改善糖尿病大鼠下肢缺血性足溃疡的愈合情况，其作用机制可能通过提升HIF-1α及其下游因子表达水平实现。 |
| 英文摘要: |
| Objective Using diabetic foot ulcers (DFU) and lower limb ischemia rat models, this study assessed the efficacy of hyperbaric oxygen therapy (HBOT) in promoting DFU healing and investigated whether the mechanism involves the activation of the hypoxia-inducible factor-1α (HIF-1α) signaling pathway and its downstream targets, vascular endothelial growth factor (VEGF) and erythropoietin (EPO). Methods A total of 18 male SD rats were randomly divided into three groups using a random number table: the normal control group (normal rats), the diabetic control group (diabetic rats), and the hyperbaric oxygen experimental group (diabetic rats receiving HBOT). After diabetic control group and hyperbaric oxygen experimental group establishing a type Ⅱ diabetes model, a dorsal foot ulcer wound was surgically created on the right lower limb under anesthesia. Additionally, the femoral artery was isolated, ligated, and transected at the thigh root to simulate an ischemic and hypoxic environment. All rats were observed for 5 days post-surgery, after which the hyperbaric oxygen experimental group underwent a 5-day HBOT regimen. During the experiment, the temperature difference between the bilateral hind limbs and ulcer healing status of the three groups of rats were observed and recorded. After HBOT intervention, hematoxylin-eosin (HE) staining was performed on ulcer tissues to detect pathological changes. Immunohistochemistry was used to analyze the expression of HIF-1α, VEGF, and EPO. Western blot was applied to determine the relative protein expression levels of HIF-1α, VEGF, and EPO before and after HBOT intervention. Results Compared with the normal control group and the diabetes control group, the hyperbaric oxygen experimental group exhibited a significantly reduced mean temperature difference between bilateral hind limbs, better ulcer recovery with markedly decreased ulcer area. Histopathological examination revealed fibrous repair accompanied by abundant neovascularization, and significantly upregulated expression levels of HIF-1α, VEGF and EPO, indicating superior ulcer healing efficacy. In the hyperbaric oxygen experimental group, the levels of HIF-1α, VEGF and EPO were also significantly upregulated compared with those before HBOT intervention. Conclusion HBOT demonstrates improved healing of ischemic foot ulcers in the lower limbs of diabetic rats. The therapeutic mechanism of HBOT is likely mediated by the upregulation of HIF-1α and its downstream factors. |
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