髓核细胞衰老是引起椎间盘退变（IVDD）的重要原因，其机制尚不清楚。SIRT3是一种调节线粒体氧化应激的去乙酰化酶。我们的预研结果证实，SIRT3在IVDD模型中表达减少，而过表达SIRT3能减轻氧化应激引起的髓核细胞衰老。据此，我们提出假说：IVDD过程中，SIRT3表达减少，引起细胞内氧化应激水平升高，促进髓核细胞衰老，加剧IVDD。为验证该假说，本项目从细胞、组织和活体层面研究以下内容：①利用大鼠模型及临床样本，明确IVDD后SIRT3分布及表达变化；②采用shRNA干扰及基因转染技术，探究IVDD后调控SIRT3功能及表达变化的关键因子；③利用蛋白质印迹和免疫荧光染色技术，阐明调控SIRT3对髓核细胞衰老的影响及机制；④利用药物干预和过表达/沉默SIRT3，阐述调控SIRT3对IVDD的影响。期望通过本研究，阐明SIRT3与髓核细胞衰老的关系，为IVDD的防治提供新思路和新靶点。

Senescence of nucleus pulposus cells is an important cause of intervertebral disc degeneration (IVDD), and the mechanism is still unclear. Silent information regulator 2 homolog 3 (SIRT3) is a deacetylase which regulates mitochondrial oxidative stress. Our preliminary experiment results confirmed that SIRT3 expression was reduced in the IVDD model, whereas overexpression of SIRT3 attenuated senescence of nucleus pulposus cells induced by oxidative stress. Thus, we proposed a hypothesis: during the IVDD process, the expression of SIRT3 is reduced, resulting in increased intracellular oxidative stress, thereby promoting senescence of nucleus pulposus cells and aggravating IVDD. To validate our hypothesis, the project studied the following issues at the cellular, tissue, and living levels: ①using rat models and clinical samples to determine the distribution and expression of SIRT3 after IVDD; ②using shRNA interference and gene transfection techniques to explore the key factors that regulate the function and expression of SIRT3 after IVDD; ③using Western blot and immunofluorescence staining techniques to elucidate the effects and mechanisms of SIRT3 on aging of nucleus pulposus cells; ④utilizing drug intervention and overexpression/silencing of SIRT3 to elaborate the effects of SIRT3 on IVDD. It is expected that the relationship between SIRT3 and senescence of nucleus pulposus cells will be elucidated through this study, which will provide new ideas and new targets for the prevention and treatment of IVDD.