炎性刺激下髓核分泌细胞外微囊泡对髓核细胞外基质代谢的作用及机制研究

脊柱椎间盘退变是引起下腰痛及颈肩痛的最为常见的病因之一，是目前影响日常健康生活的重要因素。其治疗方式目前仍主要以手术为主，尚缺乏有效的非介入性防治手段，而这与疾病发生机制不明密切相关。近年来研究表明，细胞外囊泡能够通过影响组织微环境参与疾病的发生发展，但其在椎间盘退变中的效应尚不清楚。基于前期研究成果，本项目拟针对退变炎症环境下髓核分泌的细胞外微囊泡进行系统研究，通过比较炎性刺激微囊泡对髓核基质退变的影响明确其功能；利用高通量分析比较炎性刺激下囊泡蛋白及RNA成分的差异，并找出关键分子；通过分子实验明确其影响髓核退变的机制；最终利用构建的退变模型小鼠研究炎性刺激微囊泡以及关键分子对退变的在体影响，并尝试构建以微囊泡为载体的靶向制剂，探究其在体退变修复及预防可能性。通过该项目的实施，力求为进一步明确椎间盘退变的机制提供理论依据，同时为椎间盘退变相关疾病的诊治与预防提供新的思路。

Spinal disc degeneration is one of the most common causes of lower back pain and neck pain, and is an important factor affecting daily health. The treatment method is still mainly surgery, there is still a lack of effective non-interventional prevention and treatment means, and this is closely related to the mechanism of disease occurrence is not clear. In recent years, studies have shown that extracellular vesicles can be involved in the development of disease by affecting tissue microenvironment, but their effects in disc degeneration between vertebral stoics are not clear. Based on the prior research results, this project intends to carry out a systematic study of extracellular micro-vesicles secreted by nucleus pulposus cells in inflammatory environment. To clarify its function by comparing the effects of inflammatory stimulation micro-vesicles on nucleus pulposus matrix degeneration, to analyze the differences in the composition of the micro-vesicle protein and RNA by using high throughput between inflammatory and non-inflammatory environment, and to identify key molecules. The mechanism of its effect on nucleus pulposus degeneration will be clarified by molecular experiments, and the mechanism of nucleus pulposus degeneration was finally studied by using the constructed degenerative model mice to study the in vivo effects of inflammatory stimulation micro-vesicles and key molecules on degeneration, and to try to construct a targeted micro-vesicle carrier therapy method to explore the possibility of repair and prevention of degeneration in vivo. Through the implementation of this project, it is aimed at providing theoretical basis for further clarifying the mechanism of disc degeneration, and providing new ideas for the diagnosis and treatment and prevention of intervertebral disc degeneration-related diseases.