Complexin Ⅰ调控EVs/CXCL7分泌影响纤维瘢痕形成在脊髓损伤修复中的作用机制研究

轴突再生困难是脊髓损伤修复领域内的关键科学难题和研究热点，纤维瘢痕形成是阻碍其再生的主要因素。申请人前期研究发现，下调复合素1（Complexin Ⅰ，CPLX1）抑制神经元胞吐作用、减小纤维瘢痕面积，从而有利于轴突再生，促进神经功能恢复，但调控机制不清。已知基质细胞向损伤处迁移聚集是形成纤维瘢痕的重要基础，且预实验证实下调CPLX1抑制成纤维细胞趋化作用，同时减少EVs/CXCL7释放。基于此，本项目提出“CPLX1通过调控EVs/CXCL7介导的基质细胞向损伤部位的迁移聚集，影响纤维瘢痕形成，促进轴突再生”的假说。为验证该假说，本课题将从动物、细胞和分子水平，论证和阐述此科学假说的各个环节，阐明CPLX1对EVs/CXCL7分泌的调控机制及其对纤维瘢痕形成的影响，为临床上发掘脊髓损伤治疗策略提供新的方向及理论依据。

The difficulty of axon regeneration is a key scientific problem and research hotspot in the field of SCI repair. The formation of fibrous scar is an important factor that hinders its regeneration. Previously, we found that down-regulation of complexin I (CPLX1) reduced the exocytosis of neurons and the area of fibrous scar, which were benefit for the axon regeneration and neurobehavioral recovery. However, the regulatory mechanism is unclear. It is known that the migration and aggregation of stromal cells to the injury site is an important basis for the formation of fibrous scar. Pre-experiments confirmed that down-regulation of CPLX1 attenuated fibroblast chemotaxis and reduced the EVs/CXCL7 release. Based on this, we proposed the hypothesis that “CPLX1 affects fibrous scar formation and promotes axon regeneration by regulating EVs/CXCL7-mediated stromal cell migration and aggregation to the injury site”. In order to verify this hypothesis, this study will demonstrate all aspects of this scientific hypothesis from the animal, cellular and molecular levels, elucidate the regulatory mechanism of CPLX1 on the secretion of EVS /CXCL7 and its effect on fibrous scar formation, providing a new direction and theoretical basis for the clinical exploration of spinal cord injury therapeutic strategy.