我们前期研究证实，在脊髓损伤（SCI）局部微环境中，早期可检测到神经损害性的M1型巨噬细胞（M1细胞）和神经保护性的M2型巨噬细胞（M2细胞），但损伤一周后M1细胞占绝对优势，而M2细胞比例则很少。并首次证实采用过继免疫可以提高损伤局部M2细胞的比例，发挥神经保护作用。但是，该方法需培养细胞，有滞后性，会错过SCI早期治疗的时间窗。因此，以M1/M2细胞为靶点，寻找适合临床应用的小分子药物，才是治疗SCI的可行性策略。在SCI局部，与巨噬细胞分化相关的配体及其信号级联反应，对于药物的筛选具有重要价值，但缺少系统研究。因此，本课题拟采用RNA-Seq技术，分析SCI不同时间点以及M2细胞过继回输后，损伤局部基因在转录水平表达的变化，然后针对与M1、M2细胞分化相关的关键基因进行信号通路构建，进一步筛选、鉴定关键分子和信号通路，作为药物干预的靶点，为SCI的临床治疗提供新的理论和实验依据。

Our previous study has shown that classically activated pro-inflammatory (M1) and alternatively activated anti-inflammatory (M2) macrophages populate the local microenvironment after spinal cord injury (SCI). The former type is neurotoxic while the latter has positive effects on neuroregeneration. However, a week after SCI, M1 cells are dominant, while the M2 cells are very rare. We also confirmed that it could increase the fraction of M2 cells, prolong their residence time and play a neuroprotective role by adoptive immunotherapy. However, this is difficult to apply in a clinical setting, given that it requires time to culture cells and will be outside the time window for the early treatment of SCI. For this reason, it will be a promising strategy for the SCI repair by screening the small molecule drugs targeting M1/M2 cells. It is very important for drug screening by elucidating the ligands and their signal transduction pathway associated with macrophage differentiation in the injured local microenvironment. However, it has never been studied profoundly and systematically. Thus, in the present study, the changes in gene expression at the transcriptional level in the injury spinal cord at different time points after SCI and M2 cell adoptive transfer will be identified by RNA-Seq technology. Then, the signal pathways will be constructed based on the key genes related to M1 and M2 polarization. The key molecules and signaling pathways will be further clarified and considered to be targets for pharmacologic intervention. These explorations will provide new theoretical and experimental basis for the clinical treatment of SCI.