Zhang Xian, Zhao Song, Zhao Xiaogui, Yang Zhiwei, Wang Xiaodan
College of Traditional Chinese Veterinary Medicine of Hebei Agricultural University, 289 Lingyusi Street, Baoding City, Hebei Province, China.
JINYUBAOLING BIO-PHARMACEUTICAL Co.Ltd, 1 Jinyu Street, Shaerqin Industrial Park, Hohhot Economic and Technological Development Zone, Inner Mongolia Autonomous Region, China.
Heliyon. 2024 Feb 20;10(5):e26711. doi: 10.1016/j.heliyon.2024.e26711. eCollection 2024 Mar 15.
Diabetes serves as a severe chronic disease that severely affects the normal life of human beings. Diabetes causes the complication of diabetic wound dysfunction, which is characterized by sustained inflammation, altered angiogenesis, delayed epithelialization and abnormal secretion of protease. Dang-Gui-Bu-Xue decoction (DBD) is a Chinese traditional medicine that comprises Radix Astragali and Radix Angelicae sinensis and is widely applied in treatment of multiple diseases owing to its functions against inflammation, lipid peroxidation and oxidative stress. Nevertheless, the impact of DBD on diabetic wound healing remains elusive. In this study, we aimed to explore the function of DBD in the regulation of wound healing. We observed that the gavage administration of DBD reduced the wound area, inflammatory infiltration, inflammatory factor levesl, and enhanced granulation tissue formation, wound extracellular matrix (ECM) production, and CD31 accumulation in the diabetic rat wound model, and the co-treatment of gavage administration and the external administration of gauze containing DBD further improved the wound healing effect, while the combination of Notch signaling inhibitor DAPT ((N- [N- (3, 5-difluorophenacetyl)--alanyl]--phenylglycinet-butyl ester)) could attenuate the improvement. Regarding to the mechanism, the expression levels of Notch1, Delta-like canonical Notch ligand 4 (Dll4), Jagged1, and Hairy Enhancer of Split-1 (Hes1) were increased by DBD, while the treatment of DAPT impaired the effect in the rats. Furthermore, we found that the high glucose (HG)-inhibited viability and tube formation were induced by DBD in human umbilical vein endothelial cells (HUVECs), in which DAPT could reverse this effect. Therefore, we concluded that DBD contributed to wound healing by the activation of Notch signaling. Our finding provides new insight into the potential role of DBD in promoting diabetic wound healing.
糖尿病是一种严重的慢性疾病，严重影响人类的正常生活。糖尿病会引发糖尿病伤口功能障碍并发症，其特征为持续炎症、血管生成改变、上皮化延迟以及蛋白酶分泌异常。当归补血汤（DBD）是一种中药方剂，由黄芪和当归组成，因其具有抗炎、抗脂质过氧化和抗氧化应激的作用，被广泛应用于多种疾病的治疗。然而，DBD对糖尿病伤口愈合的影响仍不明确。在本研究中，我们旨在探讨DBD在调节伤口愈合中的作用。我们观察到，在糖尿病大鼠伤口模型中，灌胃给予DBD可减少伤口面积、炎症浸润、炎症因子水平，并增强肉芽组织形成、伤口细胞外基质（ECM）产生以及CD31聚集，而灌胃给药与含DBD纱布外用联合治疗可进一步改善伤口愈合效果，而Notch信号抑制剂DAPT（N-[N-(3,5-二氟苯乙酰基)-L-丙氨酰基]-L-苯基甘氨酸叔丁酯）的联合使用可减弱这种改善作用。关于其机制，DBD可提高Notch1、Delta样经典Notch配体4（Dll4）、Jagged1和分裂增强子1（Hes1）的表达水平，而DAPT处理可削弱大鼠体内的这种作用。此外，我们发现DBD可诱导人脐静脉内皮细胞（HUVECs）中高糖（HG）抑制的活力和管腔形成，而DAPT可逆转这种作用。因此，我们得出结论，DBD通过激活Notch信号促进伤口愈合。我们的发现为DBD在促进糖尿病伤口愈合中的潜在作用提供了新的见解。
