Department of Orthopedic, Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, China.
Pharmacy School, Jinzhou Medical University, Jinzhou, Liaoning 121000, China.
Mol Pharm. 2023 Sep 4;20(9):4453-4467. doi: 10.1021/acs.molpharmaceut.3c00062. Epub 2023 Aug 1.
This study aims to investigate the potential therapeutic effect of exosomes derived from macrophages loaded with curcumin (Exos-cur) on the healing of diabetic wounds. As a new type of biomaterial, Exos-cur has better stability, anti-inflammation, and antioxidation biological activity. In in vitro experiments, Exos-cur can promote the proliferation, migration, and angiogenesis of HUVECs (human umbilical vein endothelial cells) while reducing the ROS (reactive oxygen species) produced by HUVECs induced by high glucose, regulating the mitochondrial membrane potential, reducing cell oxidative damage, and inhibiting oxidative stress and inflammation. In the in vivo experiment, the Exos-cur treatment group had an increased percentage of wound closure and contraction compared with the diabetic wound control group. Hematoxylin-eosin staining (HE) and Masson staining showed that the Exos-cur treatment group had more advanced re-epithelialization, and the generated mature granulation tissue was rich in a large number of capillaries and newly deposited collagen fibers. Western blot and immunofluorescence analyses showed that Exos-cur can inhibit inflammation by activating the Nrf2/ARE pathway, upregulate the expression of wound healing-related molecules, promote angiogenesis, and accelerate wound healing in diabetic rats. These results show that Exos-cur has a good therapeutic effect on diabetic skin defects and provide experimental evidence for the potential clinical benefits of Exos-cur.
本研究旨在探讨载姜黄素巨噬细胞衍生外泌体(Exos-cur)对糖尿病伤口愈合的潜在治疗效果。作为一种新型生物材料,Exos-cur 具有更好的稳定性、抗炎和抗氧化生物活性。在体外实验中,Exos-cur 可促进 HUVECs(人脐静脉内皮细胞)的增殖、迁移和血管生成,同时减少由高葡萄糖诱导的 HUVECs 产生的 ROS(活性氧),调节线粒体膜电位,减少细胞氧化损伤,抑制氧化应激和炎症。在体内实验中,与糖尿病伤口对照组相比,Exos-cur 治疗组的伤口闭合和收缩百分比增加。苏木精-伊红染色(HE)和 Masson 染色显示,Exos-cur 治疗组具有更先进的再上皮化,生成的成熟肉芽组织富含大量毛细血管和新沉积的胶原纤维。Western blot 和免疫荧光分析表明,Exos-cur 通过激活 Nrf2/ARE 通路抑制炎症,上调与伤口愈合相关的分子表达,促进血管生成,并加速糖尿病大鼠的伤口愈合。这些结果表明,Exos-cur 对糖尿病皮肤缺损具有良好的治疗效果,为 Exos-cur 的潜在临床益处提供了实验依据。