糖尿病溃疡创面难愈合及修复期瘢痕增生是该病最主要的难题，前期临床实验表明生肌化瘀膏促进糖尿病溃疡愈合并减少瘢痕形成，但生肌不致成瘢的分子机制有待阐释。基质蛋白Cyr61是糖尿病溃疡愈合过程中的核心分子，通过不同结构域在创面愈合的不同阶段发挥功能，加速创面炎症消退的同时抑制纤维化，减少瘢痕形成。申请人前期实验显示生肌化瘀膏外涂糖尿病小鼠创面后上调Cyr61及c-Jun蛋白的表达。由于Cyr61是c-Jun的下游调控因子，申请人提出生肌化瘀膏通过c-Jun/Cyr61信号轴减少糖尿病溃疡修复期瘢痕形成的科学假说。本项目拟以链脲佐菌素诱导糖尿病小鼠及成纤维细胞BJ为研究对象，聚焦c-Jun/Cyr61在生肌化瘀膏治疗糖尿病溃疡过程中的关键作用，系统阐明生肌化瘀膏对c-Jun/Cyr61及下游纤维化因子的调控机制，从而丰富生肌化瘀膏“生肌不致成瘢”的科学内涵。

Wound hard to heal and scar formation in the maturation phase are main problems of diabetic ulcer, pre-studies have shown that Sheng-ji Hua-yu (SJHY) Ointment can promote the healing of diabetic ulcers with less scar formation, but the contradiction that it promotes healing while reducing scarring (Helping myogenesis without forming scar)is still difficult to be scientifically explained. Matrix protein Cyr61 is a key molecule in the process of diabetic ulcer healing. Cyr61 serves distinct functions at different phases in wound healing through distinct structural domains that both accelerate inflammation resolution and dampen fibrosis and reduce scarring. Applicant’s previous experiments showed that SJHY Ointment upregulated the expression of Cyr61 and c-Jun protein after external application of SJHY Ointment on diabetic wound healing. Since Cyr61 is the downstream regulator of c-Jun, the applicant put forward the scientific hypothesis that SJHY Ointment reduces scar formation during maturation phase of diabetic ulcer through c-Jun/Cyr61 axis. In this project, streptozotocin-induced diabetic mice and fibroblast BJ will be used as the research object to focus on the key role of c-Jun/Cyr61 in the treatment of diabetic ulcer with SJHY Ointment to systematically clarify the regulatory mechanism of SJHY Ointment on c-Jun/Cyr61 and downstream fibrosis factor, so as to enrich the scientific connotation of "Helping myogenesis without forming scar" of SJHY Ointment.