生物力学因素在SpA/AS附着端炎和新骨形成中诱导机制的影像学研究

SpA/AS is autoimmune disease involving in the spine and peripheral joints, which is commonly seen in the clinical setting. Early diagnosis is essential to prevent the disease into irreversible phase. However, the pathogenesis is not clear, and there are no effective diagnosis methods, which make the early diagnosis unachievable currently. Thus, it is very important to investigate the pathophysiological mechanism of SpA/AS from different views, and explore the imaging characteristics related to early SpA/AS, which will be helpful for early diagnosis and effective treatment of the disease.. Literature and reports have shown that entheseal disease is the most pathognomonic characteristic related to SpA/AS, including specific disease site (fibrocartilaginous enthesis) and distinctive pathogenic changes (simultaneous inflammation and new bone formation); Inflammation and new bone formation in synovio-entheseal complex driven by biomechanical stress play an important role in the development of SpA/AS. Our preliminary studies also demonstrated that enthesitis is earlier than sacroiliitis in HLA-B27 positive/immunologic adjuvant induced animal model with SpA/AS. Based on previous researches, we designed this study focusing on the induction of biomechanical stress in enthesitis and new bone formation by using animal models with pre-SpA/AS arthritis. By imaging studies of the structures, cellular function, biochemical components, blood flow and mechanical properties of synovio-entheseal complex in Achilles tendon, as compared with histopathological studies, we aim to explore effective imaging methods for the early diagnosis of SpA/AS.

SpA/AS是常见的自身免疫性脊柱关节病，早期诊断是防治其进入不可逆期的关键。目前其发病机制尚不完全清楚，缺乏有效的诊断方法。因此研究SpA/AS的机制、探索早期影像学诊断方法显得尤为重要。. 研究表明附着端病变是SpA/AS重要的特征性病理改变，包括特殊发病部位（纤维软骨型附着端）和特殊病理改变（炎症和新骨形成）；生物力学因素诱导的滑膜-附着端复合体炎症和新骨形成在SpA/AS发病机制中扮演重要作用。我们的前期研究利用HLA-B27/免疫佐剂诱导的SpA/AS动物模型，也发现了附着点炎先于骶髂关节炎这一现象。本研究拟在前期研究基础上，以Pre-SpA/AS关节炎小鼠模型，通过影像学及病理学对照研究，着重探讨生物力学因素对附着端炎症及新骨形成的诱导作用，并通过对附着端组织结构、细胞功能、生化成分、血流、力学性质的成像分析，为SpA/AS早期诊断探寻有效的影像学方法。

脊柱关节炎（Spondyloarthritis, SpA）/强直性脊柱炎（Ankylosing Spondylitis，AS）是一组以不对称性外周关节炎和中轴关节炎为特征的慢性炎性病症。其致残率高，严重影响了劳动力密集人群的身体健康，给患者家庭和社会经济带来沉重负担。早期诊断，早期治疗是延缓或逆转SpA/AS病理进程最关键的因素。然而在临床实践中，由于技术条件的限制，SpA/AS的误诊率非常高。因此，利用最新的影像学技术，无创性、可视化研究SpA/AS的发病机制和特征性的早期病理改变，找出敏感性和特异性更高的生物学标志/病理特征，在疾病早期的可逆阶段作出正确的诊断将对SpA/AS研究领域具有重要意义。. 本研究采用了TNFΔARE和DBA/1小鼠关节炎模型，通过多模态影像技术（包括破骨细胞的USPIO MR成像、附着端血供和血管通透性的定量动态增强MR成像、附着端纤维软骨细胞柱排列结构的软骨DTI成像、成骨细胞活性的18F-Fluoride PET/CT成像、附着端新骨形及矿物质分布特征的micro-CT成像、附着端纤维软骨基质生化成分的T1-mapping MR成像等）与组织病理、生理学的对照研究，探索不同生物力学条件下小鼠后肢跟腱和跖底组织的炎症改变和不同生物力学刺激条件下小鼠后肢跟腱和足底组织的新骨形成的特点。实验结果显示，生物活动的机械应力可以明显加重受累关节的炎性损伤，并诱导病变附着端新骨形成；而减少日常活动对足底、下肢关节等部位的机械应力刺激，有助于缓解症状并延缓疾病的进展。实验证实了生物力学-微损伤/修复的环境因素在SpA/AS发病机制中的“触发”作用，以及相应的病理、生理、生化及力学改变的影像学特征。另外，通过多模态磁共振技术的优化和生物标记物的对照研究，为SpA/AS的早期诊断、疗效评估建立了一套有效的影像学技术方法和流程。