生肌化瘀方萃取物通过雌激素受体促进糖尿病溃疡愈合机制研究

皮肤溃疡是糖尿病最常见的严重并发症之一，也是导致我国体表难愈性溃疡形成的首要原因，给家庭和社会造成沉重负担。“化瘀生肌法”是中医外科治疗糖尿病溃疡的重要法则。课题组前期在国家自然科学基金资助下，从临床和基础研究均证实“化瘀利于生肌”学术思想指导下的生肌化瘀方，具有显著的抗炎和愈创优势。其有效组分可上调雌激素相关基因与蛋白表达，但具体作用环节不清。在网络药理学和计算机辅助模型分子对接数据支持下，我们推测该方中激活雌激素信号通路的靶标分子，可能是生肌化瘀方的愈创物质基础之一。因此本项目拟从雌激素受体着手，利用质粒转染、Biotin生物素探针，结合微量热泳动和蛋白质组学技术，揭示生肌化瘀方萃取物治疗糖尿病溃疡的分子机制。项目研究继续深入阐释“化瘀利于生肌”学术思想，旨在突破生肌化瘀方成分繁杂研究瓶颈，解决药效物质基础不清导致的临床推广障碍核心问题，同时可为推动既往基础研究成果向临床转化奠定基础。

Skin ulcer is one of the most common serious complications of diabetes mellitus, and also causes the formation of refractory ulcer on the body surface, which places a heavy burden on families and society in China. Concept of Hua-Yu Sheng-Ji (Removing blood stasis and promoting granulation) is an important rule of TCM surgery in the treatment of diabetic ulcer. With the support of the National Natural Science Foundation of the state, we have proved that the SJHY formula under the concept of Hua-Yu Sheng-Ji has significant anti-inflammatory and wound healing effects. Its effective components can increase estrogen-related genes and protein expression, but the specific role of the link remains unclear. Supported by network pharmacology and computer-aided model molecular docking data, we speculate that the target molecule that activates the estrogen signaling pathway may provide the ideal environment for wound healing. Therefore, we plan to use plasmid transfection, biotin probe, combined with micro-thermal swimming and proteomics techniques, to reveal the molecular mechanisms of the extraction of Sheng-Ji Hua-Yu (SJHY) for the treatment of diabetic ulcer. This research will further explain the concept of ‘removing blood stasis and promoting granulation’ and clarify the complicated composition of SJHY formula as well as resolve the unknown pharmacological effect, so as to lay the foundation for the transformation of the previous basic research to the clinical application.