ROS 依赖的内质网应激-自噬反应在应力诱导髓核细胞凋亡中的作用研究

项目名称： ROS 依赖的内质网应激-自噬反应在应力诱导髓核细胞凋亡中的作用研究

项目编号： No.81501926

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： 陈江伟

作者单位： 南昌大学

项目金额： 18万元

中文摘要： 椎间盘组织的退变与椎间盘细胞的程序性死亡密切相关，而自噬作为II型程序性细胞死亡方式，在椎间盘领域的研究并不多。本课题组的前期研究证实了椎间盘细胞存在自噬现象，并且主要检测了营养剥夺、氧化应激等条件下椎间盘细胞的自噬和凋亡水平的变化。而与生物学因素相比，力学因素在椎间盘退变过程中的作用可能更为关键。本课题组在成骨细胞中的研究中发现，氧化应激对自噬的诱导是通过激活内质网应激途径，并且是依赖于ROS的。因此我们对压应力下髓核细胞自噬和凋亡的变化，以及ROS依赖的内质网应激途径在其中的作用很感兴趣。本研究拟在人体标本、动物模型、细胞水平检测自噬和椎间盘退变的关系，并通过基因技术或应用阻断剂明确ROS依赖的内质网应激-自噬反应在应力诱导的髓核细胞凋亡中的作用，为最终阐明椎间盘退变的病理机制提供理论基础和实验依据。

中文关键词： 自噬；凋亡；内质网应激；活性氧自由基；应力

英文摘要： Programmed cell death plays a crucial role in the process of intervertebral disc degeneration. The research on autophagy, as type II programmed cell death, in the area of intervertebral disc degeneration is not much. Our earlier research confirmed the presence of autophagy in the intervertebral disc cell. And we mainly focused on the changes of autophagy and apotosis level in the conditions of nutritional deprivation and oxidative stress in the past. While, mechanical stress might play a more important role in the intervertebral disc degeneration, compared with those biological factors. Our earlier research also found that oxidative stress induced autophagy in the osteoblast through the endoplasmic reticulum stress pathway, which was ROS dependent. So we were interested in the effect of mechanical stress to the autophagy and apoptosis levels in nucleus pulposus cells, and whether the changing was through endoplasmic reticulum stress pathway and ROS dependent. Then, we investigated the relation of autophagy and intervertebral disc degeneration in vitro and in vivo, and explored the role of endoplasmic reticulum stress pathway in the process by RNA interference or inhibitor. This study would provide the theoretical and experimental evidence for clarifying pathogenesis of intervertebral disc degeneration, and raise a new idea for the prevention and treatment of intervertebral disc degeneration.

英文关键词： Autophagy;Apoptosis;Endoplasmic reticulum stress;ROS;Mechanical stress