Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, China.
Institute of Albert, Wenzhou Medical University, Wenzhou, China.
Eur J Pharm Sci. 2024 Dec 1;203:106923. doi: 10.1016/j.ejps.2024.106923. Epub 2024 Oct 3.
Random flaps are widely used in tissue reconstruction, but the high incidence of flap necrosis after operation remains a significant challenge. Maresin 1 (MaR1), a mediator derived from docosahexaenoic acid, has been shown to have significant effects in resolving inflammation and promoting tissue regeneration. This study investigated the role of MaR1 in the survival of random flaps. Histological analysis, laser Doppler blood flow imaging, Masson trichrome staining, and survival area analysis were used to assess the viability of the flaps. Apoptosis, ferroptosis, oxidative stress, angiogenesis, and the underlying mechanisms were explored by examining the expression of specific molecules using immunofluorescence, western blotting, and other immunological and molecular biology techniques. The findings demonstrated that MaR1 could improve flap lifespan by significantly reducing oxidative stress, apoptosis, and ferroptosis, as well as by enhancing angiogenesis. The Keap1-Nrf2 pathway was upregulated by MaR1, which inhibited ROS-mediated apoptosis and ferroptosis. The protective effect of MaR1 on flap survival was abolished by ML385. Our findings indicate that MaR1 could be a novel therapeutic agent for enhancing flap treatment outcomes.
随机皮瓣被广泛应用于组织重建，但术后皮瓣坏死的高发生率仍然是一个重大挑战。maresin 1（MaR1）是一种来源于二十二碳六烯酸的介质，已被证明在解决炎症和促进组织再生方面具有显著作用。本研究探讨了 MaR1 在随机皮瓣存活中的作用。通过组织学分析、激光多普勒血流成像、Masson 三色染色和存活面积分析评估皮瓣的存活能力。通过免疫荧光、Western blot 及其他免疫和分子生物学技术检测特定分子的表达，探讨细胞凋亡、铁死亡、氧化应激、血管生成及潜在机制。结果表明，MaR1 可通过显著降低氧化应激、细胞凋亡和铁死亡，以及增强血管生成来延长皮瓣的存活时间。MaR1 上调 Keap1-Nrf2 通路，抑制 ROS 介导的细胞凋亡和铁死亡。ML385 可消除 MaR1 对皮瓣存活的保护作用。我们的研究结果表明，MaR1 可能成为一种增强皮瓣治疗效果的新型治疗药物。
