GAD基因修饰神经干细胞在创伤性颅脑损伤大鼠中的作用

Neural stem cells modified by GAD in treatment of rat traumatic brain injury

目的探讨移植谷氯酸脱羧酶(GAD)基因修饰的神经干细胞(Neural Stem Cells,NSCs)在创伤性颅脑损伤(TBI)大鼠中的作用。方法将40只雄性SD大鼠随机分成4组,每组10只。利用电穿孔转染大鼠NSCs,通过脑立体定向仪分别将GAD转基因NSCs(GAD+NSCs组)、NSCs(NSCs组)、磷酸盐缓冲液(PBS,PBS组)移植到TBI大鼠局部损伤灶附近,通过TUNEL法检测NSCs的凋亡情况,对照组大鼠不做处理,并进行神经损坏严重程度评分(neurological severity score,NSS)对移植后大鼠的神经系统行为和运动功能进行评估。结果NSS结果显示GAD+NSCs组和NSCs组在第10、20、30天神经功能评分均低于PBS组(P<0.05);GAD+NSCs组在第10和20天神经功能评分低于NSCs组(P<0.05);在转基因NSCs移植7d后神经细胞凋亡数明显最少。结论转基因NSCs移植后合成GDA能够促进TBI大鼠神经功能的恢复。

Objective To investigate the effect of neural stem cells （NSCs） modified by glutamic acid decarboxylase （GAD） on rat traumatic brain injury. Methods GAD-transfected neural stem cells （GAD＋NSCs group）, wild neural stem cells （NSCs group） and PBS （PBS group） were transplanted into rats with traumatic brain injury. Neurological function was assessed by neurological severity score （NSS） in all groups after transplantation. TUNEL was employed to observe the cell apoptosis. Results The values of NSS in GAD＋NSCs and NSCs groups were significantly lower than that of PBS group at 10h, d20 and d30 after cell transplantation（P〈0.05）. The NSS scores in GAD＋NSCs group were lower than those in NSCs group at d20 and d30（P〈0.05）. At each time point, the rate of cell apoptosis in transplantation group was lower than that in model group （P〈0.05）. Conclusion Neural stem cells modified by GAD can protect neural function in rats with traumatic brain injury.