神经干细胞移植联合氨基甲酰促红细胞生成素对脑瘫大鼠的作用及机制

Effects of combined transplantation of neural stem cells and carbamylated erythropoietin on neonatal rats with cerebral palsy

目的研究神经干细胞（NSCs）移植联合氨基甲酰促红细胞生成素（CEPO）对新生脑瘫大鼠脑损伤的保护作用。方法从孕14～16天大鼠获得神经干细胞，经过培养并传代后备用。利用7日龄wistar大鼠制作脑瘫模型，给予CEPO腹腔注射和神经干细胞移植，对神经干细胞移植后的分化、凋亡情况，免疫分子在移植前后的改变，大鼠神经系统功能检测等各项指标进行评估，并与单-神经干细胞移植、CEPO腹腔注射效果进行比较。结果缺氧缺血脑损伤后，IFN-γ和IL-1β的浓度显著提高（P〈0．05），MHC的含量增加，大鼠学习能力下降（P〈0．05）。联合应用CEPO和神经干细胞移植可使移植细胞存活率提高并向神经元分化，降低血中IFN-γ和IL-1β水平，调节MHC抗原的表达,进而明显改善大鼠的神经运动功能。结论应用CEPO可促进移植细胞存活，调节免疫分子的分泌，改善细胞存活的环境，对移植细胞具有明显的保护作用。

Objective To investigate effects of combined transplantation of neural stem cells and car-bamylated erythropoietin （CEPO） on neonatal rats with cerebral palsy, and. discuss the underlying mechanisms of treating central nervous system injuries. Methods We utilized neonatal rats with cerebral palsy, at different time points, CEPO was given by intraperitoneal injection, or NSCs were transplanted in ventricle ,or NSCs trans-plantation was combined with CEPO. The differentiation and apoptosis of NSCs, and the changing of inflamma-tion cytokines and immune molecules were investigated. Neurological functions were assessed and compared with single NSCs transplantation or CEPO injection to explore the possible better way of treatment. Results The NSCs were successfully cultured. In neonatal rats with cerebral palsy,result of ELISA showed that IFN-γ and IL-1 β were increased in serum, while CEPO could decrease their levels. In transplanted ones, both MHC-Ⅰ and MHC-Ⅱ were increased, and down-regulated when CEPO was administered. Moreover,the combination of CEPO injection and NSCs transplantation could accelerate neurological recovery and the survival and differentiation to neurons of transplanted cells. Conclusions In neonatal rats with cerebral palsy, combination of CEPO and NSCs transplantation promoted survival and differentiation of NSCs, and decreased the level of IFN-γ and IL-1β in serum, and regulated MHC expressions, and then promoted neurological recovery.