脑外源性神经因子基因修饰神经干细胞对脑卒中的神经保护机制

Neuroprotective effect of neural stem cells modified by glial-derived neurotrophic factor on cerebral apoplexy

背景:脑外源性神经因子-胶质源性神经营养因子对大脑神经元具有特异性的营养作用,是脑卒中治疗中重要的神经营养因子。目的:探讨胶质源性神经营养因子基因修饰的神经干细胞对大鼠脑卒中的神经保护作用机制。方法:构建大鼠胶质源性神经营养因子基因pA d Easy-l-p AdT rack CMV重组体,并对新生大鼠皮质神经干细胞进行分离、培养。利用胶质源性神经营养因子基因重组腺病毒对神经干细胞进行转染,再将细胞悬液注射至暂时性(2 h)大脑中动脉缺血模型大鼠右侧脑室中,同时设单纯神经干细胞组和对照组进行对比。结果与结论:与神经干细胞移植组比较,联合移植组再灌注2,3周的神经功能缺损评分,再灌注7 d脑缺血损伤面积均显著减小(P<0.05);不同再灌注时间点缺血区域的神经干细胞数量神经干细胞移植组均显著少于联合移植组(P<0.05)。再灌注7,14 d,两组Syn,PSD-95蛋白表达均高于对照组(P<0.05),联合移植组升高较为明显。结果表明,利用经胶质源性神经营养因子基因修饰的神经干细胞治疗大鼠脑卒中可以发挥出较好的神经保护作用,效果略优于单纯神经干细胞治疗。

BACKGROUND： Glial-derived neurotrophic factor has a specific effect on brain neurons, and is an important neurotrophic factor in the treatment of cerebral apoplexy.OBJECTIVE： To investigate the neuroprotective effect of glial-derived neurotrophic factor gene modified neural stem cells on rat cerebral apoplexy. METHODS： The recombinant human plasmid p Ad Easy-l-pAdTrackCMV was constructed, and the neural stem cells were isolated and cultured from the cortex of neonatal rats. The neural stem cells were transfected with the recombinant adenovirus of glial-derived neurotrophic factor, and the cell suspension was injected into the right brain ventricle of rats with transient cerebral ischemia（2 hours）. Meanwhile, neural stem cell transplantation group and control group were set up. RESULTS AND CONCLUSION： Compared with the neural stem cell transplantation group, the modified neurological severity score of combined transplantation group was reduced significantly 2 and 3 weeks after reperfusion, and the area of cerebral ischemia injury was also significantly decreased at 7 days after reperfusion（P〈0.05）. The number of neural stem cells in the neural stem cell transplantation group was significantly less than that in the combined transplantation group（P〈0.05）. The expression of Syn, PSD-95 proteins in the two transplantation groups, especially in the combined transplantation group, was higher than that of the control group（P〈0.05）. However, there was no significant difference between the two transplantation groups（P〉0.05）. The results show that the neural stem cells modified by glial-derived neurotrophic factor can play a better role in the neuroprotection against cerebral apoplexy in rats, and the effect is better than that of simple neural stem cells.