Intractable wound healing is the habitual problem of diabetes mellitus. High blood glucose limits wound healing by interrupting inflammatory responses and inhibiting neoangiogenesis. Oxidative stress is commonly thought to be a major pathogenic cause of diabetic complications. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one, EDV) is a free radical scavenger which suppress oxidative stress. This study investigates whether EDV can reduce oxidative stress in wound healing HaCaT/human dermal fibroblasts cells (HDFs) in vitro and in vivo animal model. Cell viability and wound healing assays, FACS flow cytometry, and Hoechst 33342 staining were performed to confirm apoptosis and cytotoxicity in H₂O₂ and EDV-treated HaCaT and HDFs. A streptozotocin-induced hyperglycemic animal model was made in adult C57BL6 mice. Full-thickness skin flap was made on dorsomedial back and re-sutured to evaluate the wound healing process. EDV was delivered slowly in the skin flap with degradable fibrin glue. The flap was monitored and analyzed on postoperative days 1, 3, and 5. CD31/DAPI staining was done to detect newly formed blood vessels. The expression levels of NF-κB, bcl-2, NOX3, and STAT3 proteins in C57BL6 mouse tissues were also examined. The wound healing process in hyper- and normoglycemic mice showed a difference in protein expression, especially in oxidative stress management and angiogenesis. Exogenous H₂O₂ reduced cell viability in a proportion to the concentration via apoptosis. EDV protected HaCaT cells and HDFs from H₂O₂ induced reactive oxygen species cell damage and apoptosis. In the mouse model, EDV with fibrin resulted in less necrotic areas and increased angiogenesis on postoperative day 5, compared to sham-treated mice. Our results indicate that EDV could protect H₂O₂-induced cellular injury via inhibiting early apoptosis and inflammation and also increasing angiogenesis. EDV might be valuable in the treatment of diabetic wounds that oxidative stress has been implicated.

难治性伤口愈合是糖尿病的常见问题。高血糖通过中断炎症反应和抑制新血管生成来限制伤口愈合。氧化应激通常被认为是糖尿病并发症的主要致病原因。 Edaravone（3-甲基-1-苯基-2-吡唑啉-5-酮，EDV）是一种自由基清除剂，可抑制氧化应激。本研究探讨 EDV 是否可以在体外和体内动物模型中减少 HaCaT/人真皮成纤维细胞 (HDF) 伤口愈合中的氧化应激。进行细胞活力和伤口愈合测定、FACS 流式细胞术和 Hoechst 33342 染色，以确认 H ₂ O ₂和 EDV 处理的 HaCaT 和 HDF 中的细胞凋亡和细胞毒性。在成年 C57BL6 小鼠中制作链脲佐菌素诱导的高血糖动物模型。在背内侧制作全层皮瓣并重新缝合以评估伤口愈合过程。使用可降解纤维蛋白胶将 EDV 缓慢输送到皮瓣中。在术后第 1 天、第 3 天和第 5 天对皮瓣进行监测和分析。进行 CD31/DAPI 染色以检测新形成的血管。还检测了 C57BL6 小鼠组织中 NF-κB、bcl-2、NOX3 和 STAT3 蛋白的表达水平。高血糖和正常血糖小鼠的伤口愈合过程显示出蛋白质表达的差异，特别是在氧化应激管理和血管生成方面。外源性 H ₂ O ₂通过细胞凋亡以与浓度成比例的方式降低细胞活力。 EDV保护HaCaT细胞和HDF免受H ₂ O ₂诱导的活性氧细胞损伤和凋亡。 在小鼠模型中，与假治疗小鼠相比，术后第 5 天，含有纤维蛋白的 EDV 导致坏死区域减少，血管生成增加。我们的结果表明，EDV 可以通过抑制早期细胞凋亡和炎症以及增加血管生成来保护 H ₂ O ₂诱导的细胞损伤。 EDV 在治疗与氧化应激有关的糖尿病伤口方面可能很有价值。