骨髓间充质干细胞衍生的外泌体通过NRF2介导的抗氧化应激促进大鼠随机皮瓣的存活

IF 2.2 3区 医学 Q2 SURGERY
Lin Zhu, Qifang Niu, Delong Li, Mozi Li, Wenwen Guo, Zhengxue Han, Yang Yang
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引用次数: 0

摘要

背景:随机皮瓣是头颈部肿瘤和创伤整形外科最常用的缺损修复方法。皮瓣的远端往往会发生氧化应激(OS),最终导致皮瓣坏死。干细胞外泌体具有抗炎、再生和抗氧化的潜在作用。核因子红细胞-2相关因子2(Nrf2)是调节氧化平衡的重要因子。据报道,外泌体可监测其转录以减轻操作系统。本研究探讨了骨髓间充质干细胞外泌体(BMSCs-Exo)抗氧化作用对随机皮瓣的影响及其内在机制:方法:在随机皮瓣手术后的第0、1和2天,将骨髓间充质干细胞外泌体注入大鼠尾静脉。第 3 天对大鼠实施安乐死,以计算存活率。采用免疫组化染色、Western 印迹、二氢乙啶探针、超氧化物歧化酶和丙二醛检测试剂盒检测 OS 水平。人脐静脉内皮细胞与 BMSCs-Exo 和 ML385(一种 Nrf2 抑制剂)在体外共同培养:结果:BMSCs-Exo可通过减少细胞凋亡、炎症和OS,同时增加血管生成,从而显著提高随机皮瓣的存活率。此外,BMSCs-Exo 还能提高线粒体膜电位,降低体外活性氧水平。这些治疗效果可能源于Keap1/Nrf2信号通路的激活:结论:BMSCs-Exo可通过调节keap1/Nrf2信号通路提高组织的抗氧化能力。BMSCs-Exo可能是解决随机皮瓣坏死问题的一种新策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Bone Marrow Mesenchymal Stem Cells-derived Exosomes Promote Survival of Random Flaps in Rats through Nrf2-mediated Antioxidative Stress.

Background:  Random flaps are the most used defect repair method for head and neck tumors and trauma plastic surgery. The distal part of the flap often undergoes oxidative stress (OS), ultimately leading to flap necrosis. Stem cells' exosomes exhibit potential effects related to anti-inflammatory, regenerative, and antioxidant properties. Nuclear factor erythroid-2-related factor 2 (Nrf2) is an important factor in regulating oxidative balance. Exosomes have been reported to monitor its transcription to alleviate OS. This study examined the impacts and underlying mechanisms of antioxidant actions of exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exo) on random flaps.

Methods:  BMSCs-Exo were injected into the tail veins of rats on days 0, 1, and 2 after surgery of random flaps. The rats were euthanized on day 3 to calculate the survival rate. Immunohistochemical staining, western blotting, dihydroethidium probe, superoxide dismutase, and malondialdehyde assay kits were used to detect the OS level. Human umbilical vein endothelial cells were cocultured with BMSCs-Exo and ML385 (an inhibitor of Nrf2) in vitro.

Results:  BMSCs-Exo may significantly improve the survival rate of the random flaps by reducing apoptosis, inflammation, and OS while increasing angiogenesis. Besides, BMSCs-Exo can also increase mitochondrial membrane potential and reduce reactive oxygen species levels in vitro. These therapeutic effects might stem from the activation of the Kelch-like enyol-CoA hydratase (ECH)-associated protein 1 (Keap1)/Nrf2 signaling pathway.

Conclusion:  BMSCs-Exo improved the tissue antioxidant capacity by regulating the Keap1/Nrf2 signaling pathway. BMSCs-Exo may be a new strategy to solve the problem of random flap necrosis.

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来源期刊
CiteScore
4.50
自引率
28.60%
发文量
80
审稿时长
1 months
期刊介绍: The Journal of Reconstructive Microsurgery is a peer-reviewed, indexed journal that provides an international forum for the publication of articles focusing on reconstructive microsurgery and complex reconstructive surgery. The journal was originally established in 1984 for the microsurgical community to publish and share academic papers. The Journal of Reconstructive Microsurgery provides the latest in original research spanning basic laboratory, translational, and clinical investigations. Review papers cover current topics in complex reconstruction and microsurgery. In addition, special sections discuss new technologies, innovations, materials, and significant problem cases. The journal welcomes controversial topics, editorial comments, book reviews, and letters to the Editor, in order to complete the balanced spectrum of information available in the Journal of Reconstructive Microsurgery. All articles undergo stringent peer review by international experts in the specialty.
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