BNIP3L/NIX介导的线粒体自噬在压力诱导椎间盘退行性变中的作用及机制

项目名称： BNIP3L/NIX介导的线粒体自噬在压力诱导椎间盘退行性变中的作用及机制

项目编号： No.81501924

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 马凯歌

作者单位： 华中科技大学

项目金额： 18万元

中文摘要： 椎间盘退行性变与椎间盘内髓核细胞数目的减少密切相关。研究显示自噬、凋亡是过度压力诱导髓核细胞减少的重要原因，但椎间盘退行性变的确切机制目前尚未阐明。前期研究中我们发现过度压力可以通过线粒体途径诱导髓核细胞凋亡，及过度压力刺激可引起髓核细胞内产生大量活性氧，从而激活细胞自噬。且首次发现线粒体自噬参与压力诱导髓核细胞损伤，压力刺激可引起髓核细胞线粒体表面蛋白BNIP3L/NIX表达增多，而BNIP3L/NIX与线粒体自噬密切相关。因此本研究将通过体内外实验进一步明确BNIP3L/NIX介导的线粒体自噬在椎间盘退行性变中的作用机制，及其与髓核细胞凋亡关系，并通过干预该通路关键蛋白调节线粒体自噬预防细胞损伤，增强细胞抵抗压力刺激能力。本研究的完成，可以从机理方面阐明过度压力如何诱导髓核细胞线粒体自噬，并为调节压力诱导髓核细胞损伤提供调控途径及靶点，这些将为椎间盘退行性变防治提供全新的思路。

中文关键词： 椎间盘退变；压力；线粒体自噬；BNIP3L/NIX；细胞凋亡

英文摘要： Interverterberal disc degeneration (IVDD) is the main reasons of low back pain. The decrease of nucleus pulposus (NP) cells is highly correlated with IVDD. Although we have known that autophagy and apoptosis are involved in the decrease of NP cells during compression-induced IVDD, the exact mechanism of IVDD is unclear. We have reported that the mitochondrial pathway is involved in compression-induced apoptosis of NP cells and autophagy is activated in compression-induced cell degeneration and is mediated by reactive oxygen species in NP cells exposed to compression. Recently, we found that mitophagy was associatied with compression-induced IVDD, the expression of BNIP3L/NIX genes were increased obviously when NP cells were exposed to compression. BNIP3L/NIX is closely related to the mitophagy. We will further study the mechanisms of compression-induced IVDD, reveal the function and mechanism of NP cell mitophagy in vivo and in vitro experiments. And the target proteins of BNIP3L/NIX mediated signaling pathway will be found to adjust NP cell mitophagy. The study will attempt to enhance the capacity of NP cell resistant to mechanical stress by adjusting the selective mitophagy. The target proteins may become the potential targets of IVD degeneration treatment. The study will provide brand new ideas and methods for the prevention and treatment of IVDD.

英文关键词： interverterberal disc degeneration;compression;mitophagy ;BNIP3L/NIX;cell apoptosis