我们前期研究表明：脊髓损伤（SCI）后，局部微环境中损害性的免疫细胞亚群和细胞因子均占优势，但具体机制不清。近年研究表明：SCI后炎症小体能够识别宿主来源的损伤相关分子模式，通过一系列反应活化IL-1β、IL-18等，导致下游炎症级联反应。但其对局部免疫微环境的影响未见报道。我们的预实验表明：损伤脊髓中确实有炎症小体相关分子的表达和活化，在局部浸润的T细胞上也可检测到IL-1β和IL-18受体的表达。体外研究也证实，炎症小体影响多种免疫细胞亚群的分化。因此，我们推测炎症小体活化与局部免疫微环境不利于SCI修复有关。本研究拟首先采用大鼠SCI模型，分别给予不同炎症小体相关靶点的特异性阻断剂，确定其有效性；然后，选择有效的阻断剂联合应用，结合免疫学、组织病理学、分子生物学等，明确炎症小体对SCI局部免疫微环境的影响；最后，确定是否可以通过抑制炎症小体活化改善局部免疫微环境、发挥神经保护作用。

Our previous study has shown that the destructive immune cell subsets and cytokines are predominant in the local microenvironment after spinal cord injury (SCI). However, the mechanism is still not elucidated. Recent studies suggest that in the injured spinal cords, inflammasome can activate inflammatory caspases and cytokines of the IL-1 family (IL-1β and IL-18) by identifying host derived damage-associated molecular patterns. However, their influence on the local immune microenvironment is rarely reported. Our preliminary experiments showed that the expression and activation of inflammasome related molecules, such as IL-1β and IL-18, could be detected in the injured spinal cord, and the expressions of IL-1β and IL-18 receptors could also be detected on the infiltrated T cells. In vitro studies have also shown that they affect the differentiation of multiple immune cell subsets. Therefore, we hypothesized that the activation of inflammasome may be related to the damage of local immune microenvironment to the injured spinal cords. In this study, the rat SCI model will be firstly given specific multi-targets blocking agents to determine their effectiveness; then, the effective blockers will be selected and used in combination, the immunology, pathology, molecular biology and other methods will be combined to make clear the effects of inflammasome on local immune microenvironment of injured spinal cords; finally, to determine whether can provide neuroprotection to injured spinal cords by inhibition of inflammasome activation and improving local immune microenvironment.