用血清蛋白组学结合多模态MRI技术探讨椎间盘源性下腰痛的新型诊断

Armed to the problem of diagnosis with discogenic low back pain, based on the heterogeneity of nucleus pulposus, we would use two-dimensional gel electrophoresis and time-of-flight mass spectrometry, SELDI-TOF MS protein chip to detect the differences of serum protein fingerprint expression of patients with discogenic low back pain, to screen serum markers. Using enhanced Scan MRI to evaluate intervertebral disc degeneration, endplate fracture and disc vascularization, using imaging technology of magnetic resonance diffusion weight and diffusion tensor to analyze disc degeneration and micro-structural changes, using magnetic resonance hydrogen proton spectroscopy (1H-MRS) to assess intradiscal metabolites, N-acetyl aspartic acid (NAA), creatine (CT), choline (Cho). To preparing antibody according to the different polypeptide, to establish the ELISA method, combining with the results of MRI studies, to establish the specific diagnosis. The expected results will establish a new effective diagnostic method of discogenic low back pain with simple, economical, safe, and deepen the understanding of degenerative disc disease.

针对椎间盘源性下腰痛诊断存在的问题,基于髓核异质性的病理特点,本项目采用双向凝胶电泳和飞行时间质谱技术，SELDI-TOF MS蛋白质芯片技术检测椎间盘源性下腰痛患者血清蛋白质指纹图谱表达差异，筛选椎间盘源性下腰痛特征性血清标志物。运用 MRI增强扫描评价椎间盘退变、终板断裂与椎间盘血管化之间的关系，运用磁共振弥散加权和弥散张量成像技术定量分析椎间盘退变，观察椎间盘退变微结构变化，利用磁共振氢质子波谱(1H-MRS)技术对椎间盘内的代谢产物进行评估，对N-乙酰天门冬氨酸(NAA)、肌酸(CT)、胆碱(Cho)浓度进行测量。根据所获得的差异多肽，制备免疫抗体，建立检测特定多肽的ELISA法，结合MRI技术临床研究的结果，建立新型特异的诊断，在临床上多方面多层次验证诊断方法可行性、灵敏度和特异度。预期结果将建立椎间盘源性下腰痛简便、经济、安全、有效的新型诊断方法，深化对椎间盘退变性疾病的认识。

颈腰椎退变性疾病是危害人类健康的重要疾病之一。本项目采用蛋白组学技术，对椎间盘源性下腰痛和对照组血清的差异蛋白的寻找，发现33个表达差异的蛋白，初步建立了疾病的诊断模型。椎间盘源性下腰痛血清中Caspase-1、IL-18、IL-1β呈现高表达，和疼痛症状成正相关，进一步说明它们诱发的炎症反应导致疼痛的机制。建立了射频消融和椎间孔镜联合治疗多阶段椎间盘退变的新模式，研制了预防椎间盘手术失败综合征的新药甲强龙缓释剂。这些成果对于颈腰椎退变的诊断和治疗都有重要的意义。