基于cGMP/VEGF/Notch通路研究腐尽生肌散“祛瘀生新”促进DFU创面愈合的机制

糖尿病足溃疡（Diabetic foot ulcer，DFU）致残和致死率高，在血糖与感染控制后，DFU创面依然较难愈合。经方腐尽生肌散作为“祛瘀生新”代表方剂，其主要组成药物均有治疗DFU，促进创面愈合的潜力。网络药理学分析表明，腐尽生肌散与DFU共同靶点富集在cGMP/VEGF/Notch通路的上下游，该通路与血小板的活化聚集以及血管的生成密切相关。我们提出cGMP/VEGF/Notch通路是腐尽生肌散促进DFU愈合的重要机制也是体现其“祛瘀生新”功效的科学假说”。本项目拟以cGMP/VEGF/Notch通道为核心，研究腐尽生肌散对DFU小鼠与细胞高糖模型的调控，利用经典分子生物学方法和激光散斑对比度分析成像、血小板活化聚集、内皮细胞迁移与小管形成等技术，深入研究腐尽生肌散对血小板活化聚集与血管生成的调控，阐明其药理机制，揭示本方“祛瘀生新”的科学内涵，推动中医药对DFU的外科治疗。

Diabetic foot ulcer (DFU) has a high disability and mortality rate. After the control of blood glucose and infection, the wound of DFU is still difficult to heal. As a representative prescription of “QU YU SHENG XIN” which means eliminating blood stasis and promoting tissue regeneration, the main components of “FU JIN SHENG Ji SAN” have the potential to treat DFU and promote wound healing. Network pharmacology analysis showed that the common targets of “FU JIN SHENG Ji SAN”and DFU were enriched in the upstream and downstream of cGMP/VEGF/Notch pathway, which is closely related to platelet activation, aggregation and angiogenesis. We propose that cGMP/VEGF/Notch pathway is an important target of “FU JIN SHENG Ji SAN” in promoting the healing of DFU, and it is also a scientific hypothesis reflecting its effect of eliminating blood stasis and promoting tissue regeneration. In this project, we will take cGMP/VEGF/Notch channel as the core to study the regulation of “FU JIN SHENG Ji SAN” on DFU mice and cell hyperglycemia model. By the classical molecular biological methods, laser speckle contrast analysis imaging, technologies of platelet activation and aggregation, endothelial cell migration and tubule formation, we will deeply study the regulation of “FU JIN SHENG Ji SAN” on platelet activation, aggregation and angiogenesis, clarify its pharmacological mechanism, reveal the scientific connotation of this formula to eliminate blood stasis and promoting tissue regeneration, and promote the surgical treatment of DFU with traditional Chinese medicine.