LMP-1抑制趋化因子CCL3/CCL4及其受体CCR介导的椎间盘内炎性细胞浸润作用的分子机制研究

腰痛是多种腰椎疾病的最为常见的临床表现，给社会卫生保健带来沉重的负担，因此重视腰痛的病理生理学研究具有十分重要的现实意义。既往研究表明，椎间盘退变过程中趋化因子表达升高从而引起的免疫细胞聚集、活化是发生腰痛的主要机制之一；LIM矿化蛋白-1（LMP-1）是一种多功能的蛋白分子，我们前期研究已证实LMP-1在抑制炎性因子导致的细胞外基质降解方面起着重要作用。预实验结果表明LMP-1可抑制趋化因子CCL3、CCL4的表达。基于既往研究及预实验结果，我们提出科学假设：1.LMP-1可以抑制椎间盘退变细胞模型中CCL3、CCL4的表达；2. LMP-1通过抑制CCL3、CCL4的表达，减少炎性细胞的聚集、活化，从而减少腰痛的发生；本课题拟通过以上科学假设的研究，明确LMP-1在抑制腰痛方面的具体作用机制，并在临床标本水平验证此科学假设，为将来腰痛的生物学治疗提供可能的作用靶点及方向。

Low back pain is the most common clinical manifestation of lumbar disc degenerative diseases, bringing the heavy burden on social public health care. Therefore, it is very important to place a high emphasis on pathophysiological research of low back pain. It is demonstrated that the aggregation and activation of immune cells by increased chemotactic factor expression greatly contribute to low back pain during disc degeneration.LIM Mineralization Protein-1(LMP-1) possess multiple function, and our previous studies have demonstrated LMP-1 plays an important role in suppressing inflammatory cytokines inducing intervertebral disc extracellular matrix degradation. Our preliminary studies demonstrated LMP-1 could decrease the expression of CCL3 and CCL4. Accordingly, we propose the following hypothesis: 1, LMP-1 can inhibit the chemotactic factor (CCL3 and CCL4) expression in disc degeneration; 2, LMP-1 can decrease the aggregation and activation of immune cells by inhibiting the expression of CCL3 and CCL4. The current project can elucidate the mechanism of LMP-1inhibiting low back pain and provide some action targets and direction for biological therapy of low back pain.