关键词: Cellular senescence Glutathione-doped carbon dot nanozymes Inflammation Intervertebral disc degeneration Oxidative stress Reactive oxygen species

Mesh : Intervertebral Disc Degeneration / drug therapy metabolism pathology Nucleus Pulposus / metabolism drug effects pathology Animals Oxidative Stress / drug effects Carbon / chemistry pharmacology Glutathione / metabolism Reactive Oxygen Species / metabolism Quantum Dots / chemistry Antioxidants / pharmacology Male Cellular Senescence / drug effects Cells, Cultured Humans Mitochondria / metabolism drug effects Cellular Microenvironment / drug effects Catalase / metabolism pharmacology Superoxide Dismutase / metabolism

来  源:   DOI:10.1186/s12951-024-02683-2   PDF(Pubmed)

Abstract:
The senescence of nucleus pulposus (NP) cells (NPCs), which is induced by the anomalous accumulation of reactive oxygen species (ROS), is a major cause of intervertebral disc degeneration (IVDD). In this research, glutathione-doped carbon dots (GSH-CDs), which are novel carbon dot antioxidant nanozymes, were successfully constructed to remove large amounts of ROS for the maintenance of NP tissue at the physical redox level. After significantly scavenging endogenous ROS via exerting antioxidant activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and total antioxidant capacity, GSH-CDs with good biocompatibility have been demonstrated to effectively improve mitochondrial dysfunction and rescue NPCs from senescence, catabolism, and inflammatory factors in vivo and in vitro. In vivo imaging data and histomorphological indicators, such as the disc height index (DHI) and Pfirrmann grade, demonstrated prominent improvements in the progression of IVDD after the topical application of GSH-CDs. In summary, this study investigated the GSH-CDs nanozyme, which possesses excellent potential to inhibit the senescence of NPCs with mitochondrial lesions induced by the excessive accumulation of ROS and improve the progression of IVDD, providing potential therapeutic options for clinical treatment.
摘要:
髓核(NP)细胞(NPCs)的衰老,这是由活性氧(ROS)的异常积累引起的,是椎间盘退变(IVDD)的主要病因。在这项研究中,谷胱甘肽掺杂碳点(GSH-CD),这是一种新型的碳点抗氧化纳米酶,在物理氧化还原水平上成功构建了去除大量ROS以维持NP组织。通过发挥抗氧化活性显著清除内源性ROS后,如超氧化物歧化酶(SOD),过氧化氢酶(CAT),谷胱甘肽过氧化物酶(GPx),和总抗氧化能力,具有良好生物相容性的GSH-CD已被证明可以有效改善线粒体功能障碍并挽救NPC的衰老。分解代谢,体内和体外炎症因子。体内成像数据和组织形态学指标,例如圆盘高度指数(DHI)和Pfirrmann等级,在局部应用GSH-CD后,IVDD的进展显着改善。总之,这项研究调查了GSH-CD纳米酶,具有抑制由ROS过度积累引起的线粒体损伤的NPCs衰老和改善IVDD进程的潜力,为临床治疗提供潜在的治疗选择。
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