MrgprB2介导的肥大细胞激活调控免疫微环境在腰椎终板Modic改变发生与发展中的作用与机制研究

终板Modic改变是腰椎退行性疾病的重要影像学表现。研究显示，退变椎间盘中有大量肥大细胞存在，而肥大细胞的激活对组织局部免疫微环境调控至关重要，肥大细胞通过趋化巨噬细胞进而激发免疫应答和炎症反应，但其对终板Modic改变发生发展的病理生理进程的影响尚无相关研究。申请人前期实验发现，人及动物腰椎终板Modic改变标本有较多激活的肥大细胞浸润，而抑制肥大细胞激活可显著抑制炎症反应。最新研究表明，MrgprB2是肥大细胞激活的新型特异性受体，然而通过MrgprB2激活的肥大细胞是否参与Modic改变发生与发展及具体作用机制尚待进一步研究。基于此，本项目在已有终板Modic改变动物模型基础上，拟用肥大细胞缺陷小鼠、MrgprB2敲除小鼠，结合细胞共培养、分子生物学等方法阐明MrgprB2介导激活的肥大细胞在腰椎终板Modic改变发生发展中的作用机制，为终板退变的逆转或修复提供理论依据。

Lumbar endplate Modic changes are important imaging manifestation of lumbar degenerative disorders. Studies have shown that plenty of mast cells exist in degenerated intervertebral discs, and the activation of mast cells is critical for the initiation and regulation of the local immune microenvironment. Mast cells stimulate immune and inflammatory responses mainly by chemotactic macrophages. However, few studies have reported that mast cells can modulate the pathophysiology of lumbar endplate Modic changes. We have found many activated mast cells infiltrated in lumbar endplate Modic changes specimens of human and animal. Studies also show that inhibiting mast cell activation can significantly suppress inflammatory responses of lumbar endplate. Recent researches indicate that MrgprB2 is a novel specific receptor activating mast cells. However, whether MrgprB2-dependent activation of mast cells participate in the initiation and progression of Modic changes remains unknown. Based on these evidences, this study intends to use mast cell-deficient mice and MrgprB2 knockout mice on the basis of the existing lumbar endplate Modic changes model, combined with cell co-culture, molecular biological detection and other methods to clarify the role of MrgprB2-dependent activation of mast cells in lumbar endplate Modic changes, then to provide a theoretical basis for the reversion or repair of lumbar endplate degeneration.