Trauma Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, Hubei, China.
J Burn Care Res. 2023 Jul 5;44(4):823-831. doi: 10.1093/jbcr/irad035.
The development of chronic, nonhealing wounds is a persistent medical problem that drives patient morbidity and increases healthcare costs. Angiogenesis is a critical accompanying activity in the proliferation stage during the wound healing process. Notoginsenoside R1 (NGR1) isolated from Radix notoginseng has been reported to alleviate diabetic ulcers by promoting angiogenesis and decreasing inflammatory responses and apoptosis. In the present study, we investigated the effect of NGR1 on angiogenesis and its therapeutic functions in cutaneous wound healing. For in vitro evaluation, cell counting kit-8 assays, migration assays, Matrigel-based angiogenic assays, and western blotting were conducted. The experimental results showed that NGR1 (10-50 μM) had no cytotoxicity to human skin fibroblasts (HSFs) and human microvascular endothelial cells (HMEC), and NGR1 treatment facilitated the migration of HSFs and enhanced angiogenesis in HMECs. Mechanistically, NGR1 treatment inhibited the activation of Notch signaling in HMECs. For in vivo analysis, hematoxylin-eosin staining, immunostaining, and Masson's trichrome staining were performed, and we found that NGR1 treatment promoted angiogenesis, reduced wound widths, and facilitated wound healing. Furthermore, HMECs were treated with N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT; a Notch inhibitor), and DAPT treatment was found to exert pro-angiogenic effects. Simultaneously, DAPT was administrated into experimental cutaneous wound healing model, and we found that DAPT administration prevented the development of cutaneous wounds. Collectively, NGR1 promotes angiogenesis and wound repair via activation of the Notch pathway and exhibits therapeutic effects on cutaneous wound healing.
慢性、难愈性伤口的形成是一个持续存在的医学难题，它会导致患者发病率上升，并增加医疗保健成本。血管生成是伤口愈合过程中增殖阶段的关键伴随活动。从三七中分离得到的三七皂苷 R1（NGR1）已被报道可通过促进血管生成、减少炎症反应和细胞凋亡来缓解糖尿病溃疡。在本研究中，我们研究了 NGR1 对血管生成的影响及其在皮肤伤口愈合中的治疗作用。在体外评估中，进行了细胞计数试剂盒-8 测定、迁移测定、基于 Matrigel 的血管生成测定和 Western blot 分析。实验结果表明，NGR1（10-50 μM）对人皮肤成纤维细胞（HSFs）和人微血管内皮细胞（HMEC）无细胞毒性，且 NGR1 处理促进了 HSF 的迁移，并增强了 HMEC 的血管生成。机制上，NGR1 处理抑制了 HMEC 中 Notch 信号的激活。在体内分析中，进行了苏木精-伊红染色、免疫染色和 Masson 三色染色，结果发现 NGR1 处理促进了血管生成、减少了伤口宽度并促进了伤口愈合。此外，用 N-[N-(3,5-二氟苯乙酰基)-L-丙氨酰]-S-苯甘氨酸叔丁酯（DAPT；Notch 抑制剂）处理 HMEC，发现 DAPT 处理具有促血管生成作用。同时，将 DAPT 给予实验性皮肤伤口愈合模型，发现 DAPT 给药可防止皮肤伤口的发展。总之，NGR1 通过激活 Notch 通路促进血管生成和伤口修复，并对皮肤伤口愈合具有治疗作用。
