Lien Wei-Chih, Yu Yu-Ling, Liang Ya-Jyun, Wang Chia-Yih, Lin Yang-Chen, Chang Huei-Cih, Lin Feng-Huei, David Wang Hui-Min
Department of Physical Medicine and Rehabilitation National Cheng Kung University Hospital College of Medicine National Cheng Kung University No. 138, Sheng Li Road Tainan 704 Taiwan (R.O.C.).
Department of Physical Medicine and Rehabilitation College of Medicine No. 1, University Road Tainan 701 Taiwan (R.O.C.).
Small Sci. 2025 Jun 26;5(8):2500208. doi: 10.1002/smsc.202500208. eCollection 2025 Aug.
Most drugs used to treat sarcopenia are ineffective. Herein, the long-acting anti-sarcopenic properties of cerium oxide nanoparticles (CeNPs) and their underlying mechanisms of action are investigated in aging mice (treated with 4-hydroperoxy cyclophosphamide (4-HC)). CeNPs (size, 27.5 nm) with a fluorite crystallization structure are synthesized and subjected to X-ray diffraction and gas adsorption analyzes. Synthesized CeNPs exhibit Ce and Ce on their surfaces, a specific surface area within the standard range, and self-regenerative antioxidative functions. Synthesized CeNPs reduce reactive oxygen species (ROS) levels and exhibit good biocompatibility in muscle satellite (C2C12) cells. According to Rotarod, tensile, and histological analyzes, CeNP treatment once per week in 4-HC-treated mice markedly increases muscle strength and the cross-sectional muscle tissue area relative to that in control mice. Next-generation sequencing identifies CILP2 as a key differentially upregulated gene common to aging muscle tissues and satellite cells in the presence of ROS. Quantitative polymerase chain reaction and western blotting confirm CILP2, Serpine1, phospho-p21, Atrogin-1, and Cxcl10 downregulation in CeNP-treated mice (compared with 4-HC-treated mice); in vitro CILP2 knockdown results in Serpine1 and phospho-p21 downregulation. These findings confirm the long-acting effects of CeNPs against sarcopenia in older individuals.
大多数用于治疗肌肉减少症的药物都无效。在此，研究了氧化铈纳米颗粒（CeNPs）的长效抗肌肉减少症特性及其潜在作用机制，研究对象为衰老小鼠（用4-氢过氧环磷酰胺（4-HC）处理）。合成了具有萤石结晶结构的CeNPs（尺寸为27.5nm），并对其进行了X射线衍射和气体吸附分析。合成的CeNPs在其表面呈现Ce和Ce，比表面积在标准范围内，且具有自我再生抗氧化功能。合成的CeNPs可降低活性氧（ROS）水平，并在肌肉卫星（C2C12）细胞中表现出良好的生物相容性。根据转棒试验、拉伸试验和组织学分析，相对于对照小鼠，在4-HC处理的小鼠中每周一次CeNP治疗可显著提高肌肉力量和肌肉组织横截面积。下一代测序确定CILP2是衰老肌肉组织和存在ROS时卫星细胞中共同差异上调的关键基因。定量聚合酶链反应和蛋白质印迹证实CeNP处理的小鼠（与4-HC处理的小鼠相比）中CILP2、丝氨酸蛋白酶抑制剂1、磷酸化p21、Atrogin-1和Cxcl10下调；体外敲低CILP2导致丝氨酸蛋白酶抑制剂1和磷酸化p21下调。这些发现证实了CeNPs对老年人肌肉减少症的长效作用。
