Cuprous oxide nanoparticles reduces hypertrophic scarring by inducing fibroblast apoptosis
Cuprous oxide nanoparticles reduces hypertrophic scarring by inducing fibroblast apoptosis
复制标题
氧化亚铜纳米颗粒通过诱导成纤维细胞凋亡来减少增生性疤痕
DOI：
10.2147/ijn.s196794
复制
发表时间：
2019-01-01
影响因子：
8
通讯作者：
Xia, Zhaofan
中科院分区：
文献类型：
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作者：
Xiao, Yongqiang;Xu, Dayuan;Xia, Zhaofan
研究背景增生性瘢痕形成过程中成纤维细胞的过度生长和细胞凋亡减少是导致瘢痕形成的重要因素。氧化亚铜纳米颗粒不仅可以通过诱导肿瘤细胞的凋亡和抑制肿瘤细胞的增殖来抑制肿瘤生长，而且还可以促进伤口的愈合。本研究的目的是进一步探讨CONPs在体内外对增生性瘢痕形成的治疗作用。方法在新西兰大白兔体内建立兔耳瘢痕模型。每耳制作6个全厚圆形创面(直径10 mm)。在术后第14天观察到完全上皮化后，在创面内注射CONPs或5%葡萄糖溶液。每周拍摄创面照片和B超，第35天取瘢痕作组织形态计量学分析。体外培养条件下，采用隧道法、Annexin V/PI染色、细胞周期分析和EDU增殖实验等方法检测CONPs对人增生性瘢痕成纤维细胞(HSFs)凋亡和增殖的影响。用透射电子显微镜观察成纤维细胞对CONPs的内吞作用，并检测线粒体膜电位和ROS的产生。结果体内注射CoNPs可明显改善瘢痕形态和胶原排列，降低瘢痕抬高指数(SEI)。在体外，CONPs能显著抑制HSFs的增殖并诱导其凋亡，且呈浓度依赖关系。此外，CONPs还可以内吞到线粒体内，破坏线粒体膜电位，增加ROS的产生。结论CONPs通过抑制HSFs增殖，诱导HSFs凋亡，具有治疗增生性瘢痕的潜力。
Background Less apoptosis and excessive growth of fibroblasts contribute to the progression of hypertrophic scar formation. Cuprous oxide nanoparticles (CONPs) could have not only inhibited tumor by inducing apoptosis and inhibiting proliferation of tumor cells, but also promoted wound healing. The objective of this study was to further explore the therapeutic effects of CONPs on hypertrophic scar formation in vivo and in vitro. Methods In vivo, a rabbit ear scar model was established on New Zealand albino rabbits. Six full-thickness and circular wounds (10 mm diameter) were made to each ear. Following complete re-epithelization observed on postoperative day 14, an intralesional injection of CONPs or 5% glucose solution was conducted to the wounds. The photo and ultrasonography of each wound were taken every week and scars were harvested on day 35 for further histomorphometric analysis. In vitro, the role of CONPs in human hypertrophic scar fibroblasts (HSFs) apoptosis and proliferation were evaluated by Tunnel assay, Annexin V/PI staining, cell cycle analysis, and EdU proliferation assay. The endocytosis of CONPs by fibroblasts were detected through transmission electron microscopy (TEM) and the mitochondrial membrane potential and ROS production were also detected. Results In vivo, intralesional injections of CONPs could significantly improve the scar appearance and collagen arrangement, and decreased scar elevation index (SEI). In vitro, CONPs could prominently inhibit proliferation and induce apoptosis in HSFs in a concentration-dependent manner. In addition, CONPs could be endocytosed into mitochondria，damage the mitochondrial membrane potential and increase ROS production. Conclusion CONPs possessed the therapeutic potential in the treatment of hypertrophic scar by inhibiting HSFs proliferation and inducing HSFs apoptosis.