脊髓损伤（SCI）是一种严重致残性疾病，早期治疗策略中阻止继发性损伤十分关键，其中抑制神经元凋亡是重要的干预目标。CircRNA是一类新发现的非编码类RNA，调节广泛的生理活动和病理变化，但目前尚未明确circRNA是否参与调控SCI诱导的脊髓神经元凋亡及潜在的作用机制。本课题在前期建立SCI大鼠模型、细胞模型，进行凋亡检测、基因芯片筛选、PCR验证、生物信息学分析的基础上拟明确：1）circNalcn、miR-223-3p、Hsp90b1基因表达水平与SCI诱导的脊髓神经元凋亡之间的关系；2）circNalcn内源性竞争miR-223-3p的分子机制；3）circNalcn抑制miR-223-3p上调靶基因Hsp90b1通过调控Akt通路抑制SCI诱导的脊髓神经元凋亡的作用机制。希望为揭示SCI诱导的脊髓神经元凋亡的分子机制提供新的理论依据，从而提供基于circNalcn的新的治疗策略。

Spinal cord injury(SCI) is a serious deformitive disease which usually brings permanent nerve damage and huge social and personal burdens. It’s a very critical treatment strategy to prevent the progression of secondary injury after spinal cord injury because primary damage cannot be avoided. Neuronal apoptosis is an important initiating factor in the mechanism of secondary injury. CircRNA is a newly discovered class of non-coding RNA involved in the regulation of a wide range of physiological activities and pathological changes. However, the mechanism of circRNA to regulate the neuronal apoptosis is not yet clear. On the basis of preliminary establishment of SCI rat model, cell model, TUNEL assay, flow cytometry, circRNA microarray screening, RT-qPCR and bioinformatics analysis, in vivo and in vitro we intend to clarify:1) the relationship between the expression changes of circNalcn, miR-223-3p, Hsp90b1 and the SCI-induced apoptosis of spinal cord neurons; 2) the molecular mechanism that circNalcn inhibits miR-223-3p as a competitive endogenous RNA; 3) circNalcn inhibits SCI-induced apoptosis of spinal neurons through modulating miR-223-3p/ Hsp90b1/Akt signaling pathway. We hope our work will provide a new theoretical basis to reveal the molecular mechanism of SCI-induced spinal neuronal apoptosis, which is expected to provide a new therapeutic strategy based on circNalcn.