HMGB1介导MAPKs信号通路影响椎间盘软骨终板退变过程及其机制研究

腰腿痛是骨科和疼痛科室常见疾病，是许多人活动能力下降和劳动力丧失的起因。在中老年人群中常见，近年有年轻化的趋势。目前很多学者认为椎间盘退变是腰腿痛最常见的原因，椎间盘的营养途径主要是软骨终板途径，因此软骨终板在椎间盘退变中的作用日益被重视。最近的研究发现，软骨终板退变过程中涉及多种蛋白质及细胞因子的变化，但它们之间的相互作用机理尚不明确。本项目通过复制椎间失稳导致软骨终板退变的动物模型，利用影像学、组织化学、细胞生物学、分子生物学技术等多种观察和检测手段，研究软骨终板退变过程中HMGB1通过MAPKs通路调节TNF-a、IL-1β、MMP3、VEGF等因子的表达规律，以阐明HMGB1在软骨终板退变中的作用及机理。通过阻断HMGB1及MAPKs通路，观察阻止和延缓软骨终板退变的效果，为延缓或治疗椎间盘退变提供新的思路。

Lumbocrural pain is the most common diseases in the department of orthopaedics and pain. These are the main reasons that induce decline of activity and loss of labor force in daily life. These are common in the elders, but the scale in youngth grows higher recently. To present, intervertebral disc degeneration has been considered as the most common reason in Lumbocrural pain.The nutrition of intervertebral disc was contributed by the cartilage endpalte. As a result, the important role of the cartilage endplate in intervertebral disc degeneration has been valued. In rescent researches, the process of cartilage endplate degeneration involved the homeostasis of various proteins and factors, but the underlying interlink and mechanism was still unclear. This project will establish an animal intervetebral destabilization model which may induce cartilage endplate degeneration.Based on this model, imageological, histochemical, cellular biological and molecular biologial method will be performed to exam HMGB1 regulates expression of TNF-a, IL-1β, MMP3 and VEGF by MAPKs pathway, For illustrateing their underlying regulatory mechanism. By blocking HMGB1 and MAPKs pathway, observation to prevent and delay the effect of cartilage endplate degeneration, thus apply novel therapeutic strategy in blockade or postpone of intervetebral disc degeration.