PDF(Pubmed)
Abstract：
Macrophages play a pivotal role in the healing of diabetic ulcers. The sustained elevation of glucose levels damages the insulin signaling pathway in macrophages, leading to dysfunctional macrophages that struggle to transition from pro-inflammatory (M1) to reparative (M2) states. Therefore, modulating macrophage inflammatory responses via the insulin pathway holds promise for diabetic ulcer treatment. Additionally, the presence of biofilm impedes drug penetration, and the resulting immunosuppressive microenvironment exacerbates the persistent infiltration of pro-inflammatory M1 macrophages. Therefore, we designed an array of dissolvable microneedle (denoted as NPF@MN) loaded with self-assembled nanoparticles that could deliver NPF nanoparticles, acid-sensitive NPF-releasing Protocatechualdehyde (PA) with hypoglycemic and insulin-like effects, regulating macrophage polarization to an anti-inflammatory M2 phenotype. Additionally, this study extensively examined the mechanism by which NPF@MN accelerates the healing of diabetic ulcers through the activation of the insulin signaling pathway. Through RNA-seq and GSEA analysis, we identified a reduction in the expression of pathway-related factors such as IR, IRS-1, IRS-2, and SHC. Our work presents an innovative therapeutic approach targeting the insulin pathway in diabetic ulcers and underscores its translational potential for clinical management.
摘要：
巨噬细胞在糖尿病溃疡的愈合中起关键作用。葡萄糖水平的持续升高会损害巨噬细胞的胰岛素信号通路，导致功能失调的巨噬细胞难以从促炎（M1）过渡到修复（M2）状态。因此,通过胰岛素途径调节巨噬细胞炎症反应有望治疗糖尿病性溃疡。此外,生物膜的存在阻碍了药物的渗透，所产生的免疫抑制微环境加剧了促炎M1巨噬细胞的持续浸润。因此,我们设计了一系列可溶解的微针（表示为NPF@MN），装载有自组装纳米粒子，可以提供NPF纳米粒子，酸敏感性NPF释放原儿茶醛（PA），具有降血糖和胰岛素样作用，调节巨噬细胞极化为抗炎M2表型。此外,这项研究广泛研究了NPF@MN通过激活胰岛素信号通路加速糖尿病溃疡愈合的机制。通过RNA-seq和GSEA分析,我们发现途径相关因子如IR的表达减少，IRS-1、IRS-2和SHC。我们的工作提出了一种针对糖尿病溃疡胰岛素途径的创新治疗方法，并强调了其在临床管理中的转化潜力。
