Background Diabetes significantly delays wound healing through oxidative stress, inflammation and impaired re-epithelialization that lead to defective regulation of the healing process, although the related mechanism remains unclear. Here, we aim to investigate the potential role and mechanism for the beneficial effect of betulinic acid (BA) on diabetic wound healing. Methods The molecular effect of BA on hyperglycemia-mediated gene expression, oxidative stress, inflammation and glucose uptake was evaluated in endothelial, fibroblast and muscle cells. Burn injury was introduced to streptozotocin-induced diabetic rats and BA administration through either an intraperitoneal (IP) or topical (TOP) technique was used for wound treatment. Glucose tolerance was evaluated in both muscle tissue and fibroblasts, while oxidative stress and inflammation were determined in both the circulatory system and in wound tissues. The effect of BA on the wound healing process was also evaluated. Results BA treatment reversed hyperglycemia-induced glucose transporter type 4 (GLUT4) suppression in both muscle and fibroblast cells. This treatment also partly reversed hyperglycemia-mediated suppression of endothelial nitric oxide synthase (eNOS), nuclear factor erythroid 2-related factor 2 (Nrf2) signaling and nuclear factor NFκB p65 subunit (NFκB p65) activation in endothelial cells. An in vivo rat study showed that BA administration ameliorated diabetes-mediated glucose intolerance and partly attenuated diabetes-mediated oxidative stress and inflammation in both the circulatory system and wound tissues. BA administration by both IP and TOP techniques significantly accelerated diabetic wound healing, while BA administration by either IP or TOP methods alone had a significantly lower effect. Conclusions BA treatment ameliorates hyperglycemia-mediated glucose intolerance, endothelial dysfunction, oxidative stress and inflammation. Administration of BA by both IP and TOP techniques was found to significantly accelerate diabetic wound healing, indicating that BA could be a potential therapeutic candidate for diabetic wound healing.

中文翻译：

---

白桦脂酸通过调节高血糖引起的氧化应激、炎症和葡萄糖耐受不良来加速糖尿病伤口愈合。

背景糖尿病通过氧化应激、炎症和受损的再上皮化导致愈合过程的调节缺陷显着延迟伤口愈合，尽管相关机制仍不清楚。在这里，我们旨在研究桦木酸 (BA) 对糖尿病伤口愈合的有益作用的潜在作用和机制。方法 在内皮细胞、成纤维细胞和肌肉细胞中评估 BA 对高血糖介导的基因表达、氧化应激、炎症和葡萄糖摄取的分子影响。将烧伤损伤引入链脲佐菌素诱导的糖尿病大鼠，并通过腹膜内 (IP) 或局部 (TOP) 技术使用 BA 进行伤口治疗。在肌肉组织和成纤维细胞中评估葡萄糖耐量，而在循环系统和伤口组织中都确定了氧化应激和炎症。还评估了 BA 对伤口愈合过程的影响。结果 BA 治疗逆转了肌肉和成纤维细胞中高血糖诱导的 4 型葡萄糖转运蛋白 (GLUT4) 抑制。这种治疗还部分逆转了高血糖介导的内皮细胞内皮细胞一氧化氮合酶 (eNOS)、核因子红细胞 2 相关因子 2 (Nrf2) 信号传导和核因子 NFκB p65 亚基 (NFκB p65) 激活的抑制。一项体内大鼠研究表明，BA 给药改善了糖尿病介导的葡萄糖耐受不良，并部分减轻了循环系统和伤口组织中糖尿病介导的氧化应激和炎症。通过 IP 和 TOP 技术施用 BA 显着加速糖尿病伤口愈合，而单独通过 IP 或 TOP 方法施用 BA 的效果显着降低。结论 BA 治疗可改善高血糖介导的葡萄糖耐受不良、内皮功能障碍、氧化应激和炎症。发现通过 IP 和 TOP 技术施用 BA 可显着加速糖尿病伤口愈合，表明 BA 可能是糖尿病伤口愈合的潜在治疗候选者。