过度压力作为椎间盘退行性变的主要诱因，可诱发椎间盘髓核细胞发生自噬。细胞自噬与线粒体损伤、内质网应激（ERS）等密切相关。我们前期研究发现，压力可以引起细胞内质网广泛扩张、Beclin-1基因表达上调，且ERS抑制剂可以明显降低压力诱导的细胞自噬水平，提示压力可能通过ERS-Beclin-1信号通路引起髓核细胞自噬。本课题拟在成功构建细胞可控加压模型的基础上，观察压力对ERS相关蛋白及Beclin-1途径相关蛋白表达水平的影响，探讨压力诱导髓核细胞自噬的可能机制；观察压力对ERS下游相关信号分子蛋白PERK、IRE1α表达水平的影响，揭示ERS和Beclin-1信号通路之间可能的偶联机制；研究髓核细胞自噬水平与细胞死亡之间的关系，阐明细胞自噬在椎间盘退行性变中的具体作用。本课题将有助于进一步深入研究椎间盘退行性变的分子机制，为椎间盘退行性变的早期防治提供新的思路和理论依据。

Excessive or inappropriate compressive force, which is the main cause of degenerative disc disease, can lead to autophagy of nucleus pulposus (NP) cells of intervertebral discs (IVDs). Autophagy of NP cells is closely related with mitochondrial damage as well as endoplasmic reticulum stress (ERS). According to our previous studies, we demonstrated that mechanical pressure can trigger extensive dilation of endoplasmic reticulum, and up-regulate the expression of Beclin-1, moreover, the application of ERS inhibitor significantly reduced the autophagy level of NP cells initiated by the compression. All these results indicate that mechanical stress may cause autophagy of NP cells through ERS-Beclin-1 pathway. This study is designed to investigate the possible mechanism of compression-induced autophagy of NP cells through observing the influence of mechanical stress on the expression of ERS and Beclin-1 pathway related proteins, to reveal the potential coupling mechanism between ERS and Beclin-1 pathway by identifying the influence of mechanical stress on the expression of ERS downstream signal molecule such as PERK and IRE1α, to illustrate the specific function of autophagy in degenerative disc disease by studying the relationship between autophagy and cell death. Our subject will make great contribution to further studying the mechanism of IVD degeneration, providing a new therapeutic strategy and theoretical foundation in preventing IVD degenerative disease.