BMSCs调控脊髓损伤中NLRP3炎症小体的激活及其机制研究

脊髓损伤早期的炎症反应严重程度对于脊髓损伤后期的结构和功能康复至关重要，炎症反应的发生发展和机制研究一直是本领域的研究重点。近期研究表明，NLRP3（Nod-like receptor，pyrin domain containing 3）炎症小体是内源性识别危险信号的多蛋白复合物，能够被一系列信号活化，通过其下游的Caspase-1，释放IL-1beta和IL-18引起炎症反应，导致 pyroptosis 样细胞死亡（细胞焦亡）。我们发现大鼠脊髓损伤早期阶段有NLRP3激活，其下游的Caspase-1表达增加；体外将骨髓间充质干细胞与损伤神经元共培养，可以减轻NLRP3炎症小体的激活，减少神经元死亡。在此基础上，我们拟研究NLRP3激活介导的炎症反应和细胞焦亡在脊髓损伤中的作用及其上下游信号机制，并进一步阐明骨髓间充质干细胞调控NLRP3炎症小体途径促进脊髓损伤修复再生的效应及靶分子机制。

Bone marrow mesenchymal stem cells (BMSCs) transplantation for the repair of spinal cord injury is one of the current hot topics. Exploring how to according the change of spinal cord injury microenvironment to improve the efficiency of BMSCs has important significance. Our previous experiments found that NLRP3 (Nod-like receptor, pyrin domain containing 3) mediated inflammation response was induced in the microenvironment of local injured spinal cord, which may lead to pyroptosis in the spinal cord. On the other hand, co-culture of neurons with BMSCs inhibited OGD-induced NLRP3 expression in neurons. Therefore, this present study intends to elucidate the activation of NLRP3 and signal pathway，not only at the cellular level, but also at the in vivo spinal cord injury model, to exam the inflammation response and pyroptosis , the repair of the structure and function of injured spinal cord and related molecular expressions. Furthermore, to clarify the inhibitory effects and related mechanisms of BMSCs on NLRP3 activation, as well as provide valuable theoretical guidance and experimental basis for the transplantation of BMSCs in spinal cord injury.