脊髓损伤微环境对BMSCs内质网应激反应的影响及其机制研究

骨髓间充质干细胞（BMSCs）移植修复脊髓损伤是目前的研究热点之一，探索如何根据脊髓损伤局部微环境改变的规律，提高BMSCs的修复效应具有重要意义。我们前期实验证实脊髓损伤局部微环境能够诱导BMSCs产生Calpain介导的内质网应激（ERS）反应，对移植入的BMSCs的存活、迁移和分化产生不利的影响。因此，本研究拟通过Calpain siRNA和过表达技术，获得Calpain低表达或过表达的BMSCs，并结合Calpain抑制剂的使用，在细胞水平和整体大鼠脊髓损伤模型上，阐明抑制Calpain介导的ERS反应后，将会促进BMSCs的存活、迁移、分化、以及损伤脊髓结构和功能的修复和相关分子机制。本研究将初步阐明脊髓损伤局部微环境诱导移植入BMSCs产生Calpain介导的ERS反应和机制，为提高移植BMSCs修复脊髓损伤的效果提供有价值的理论指导和实验依据。

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 Calpain mediated endoplasmic reticulum stress (ERS) was induced in BMSCs by the microenvironment of local injured spinal cord, which play a negative role on the survival, migration and differentiation of BMSCs. Therefore, this present study intends to modify Calpain gene in BMSCs by Calpain siRNA and overexpression technology, and combined with the use of Calpain inhibitors，not only at the cellular level, but also at the in vivo spinal cord injury model, to exam the survival, migration, differentiation of BMSCs, the repair of the structure and function of injured spinal cord and related molecular expressions. The present study would preliminary clarify the effect and related mechanisms of microenvironment of local injured spinal cord on transplanted BMSCs, as well as provide valuable theoretical guidance and experimental basis for the transplantation of BMSCs in spinal cord injury therapy.