Maxillofacial Surgery Department 4 of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100144, China.
Int J Mol Sci. 2023 Feb 14;24(4):3850. doi: 10.3390/ijms24043850.
The survival of free fat grafts is dependent primarily on adipose-derived stem cells (ADSCs); however, ADSCs are susceptible to oxidative stress in the recipient area. Astaxanthin (Axt) is a natural xanthophyll carotenoid with potent antioxidant properties and numerous clinical applications. To date, the therapeutic potential of Axt in fat grafting has not been explored. The purpose of this study is to investigate the effects of Axt on oxidatively stressed ADSCs. An oxidative model of ADSCs was developed to simulate the host's microenvironment. Oxidative insult decreased the protein levels of Cyclin D1, type I collagen alpha 1 (COL1A1), and type II collagen alpha 1 (COL2A1), while increasing the expression of cleaved Caspase 3 and secretion of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in ADSCs. Axt pre-treatment significantly reduced oxidative stress, increased the synthesis of an adipose extracellular matrix, alleviated inflammation, and restored the impaired adipogenic potential in the present model. Furthermore, Axt immensely activated the NF-E2-related factor 2 (Nrf2) pathway, and ML385, an inhibitor of Nrf2, could negate Axt's protective effects. Additionally, Axt alleviated apoptosis by inhibiting bcl-2-associated X protein (BAX)/Caspase 3 signaling and improving the mitochondrial membrane potential (MMP), which could also be abolished by ML385. Our results suggest that Axt may exert its cytoprotective effect on ADSCs through the Nrf2 signaling pathway and could be therapeutic in fat grafting.
游离脂肪移植的存活率主要依赖于脂肪来源的干细胞（ADSCs）；然而，ADSCs 容易受到受区的氧化应激。虾青素（Axt）是一种天然类胡萝卜素叶黄素，具有强大的抗氧化特性和许多临床应用。迄今为止，Axt 在脂肪移植中的治疗潜力尚未得到探索。本研究旨在探讨 Axt 对氧化应激 ADSCs 的影响。建立 ADSCs 的氧化模型来模拟宿主的微环境。氧化损伤降低了 ADSCs 中细胞周期蛋白 D1、I 型胶原α1（COL1A1）和 II 型胶原α1（COL2A1）的蛋白水平，同时增加了 cleaved Caspase 3 的表达和白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的分泌。Axt 预处理可显著减轻氧化应激，增加脂肪细胞外基质的合成，减轻炎症，并恢复该模型中受损的成脂潜能。此外，Axt 极大地激活了核因子 E2 相关因子 2（Nrf2）途径，Nrf2 的抑制剂 ML385 可消除 Axt 的保护作用。此外，Axt 通过抑制 bcl-2 相关 X 蛋白（BAX）/Caspase 3 信号通路和改善线粒体膜电位（MMP）来减轻细胞凋亡，而 ML385 也可以消除 Axt 的这种作用。我们的研究结果表明，Axt 可能通过 Nrf2 信号通路对 ADSCs 发挥细胞保护作用，并可在脂肪移植中发挥治疗作用。
