胶质细胞源性神经营养因子联合神经干细胞移植治疗脑室周围白质软化新生大鼠的疗效观察

目的 探讨在移植物中加入胶质细胞源性神经营养因子(glial cell line derived neurotrophic factor,GDNF),能否增强外源性神经干细胞(neural stem cells,NSCs)经脑室移植治疗脑室周围白质软化(periven-tricularleukomalacia,PVL)新生大鼠的移植效果.方法 采用E14胎鼠大脑皮质制备NSCs.2日龄新生大鼠随机分为PVL对照组(PVL组),PVL+NSCs移植组(PVL+NSCs组),PVL+NSCs移植+GDNF组(PVL+NSCs+GNDF组),假手术对照组(Sham组).Sham+NSCs移植组(Sham+NSCs组),以及Sham+NSCs移植+GDNF组(Sham+NSCs+GDNF组).对PVL新生大鼠在建模后72 h进行立体定位仪下经脑室NSCs移植,分别于移植术后7、14、21 d进行免疫荧光、光镜及电镜病理检测,评估在NSCs中加入GDNF对移植效果的可能影响.结果 经脑室植入的外源性NSCs在脑内具有良好的迁移能力,3 d内大部分移行至脑室周围,2周左右在脑室周围主要分化为少突胶质细胞前体,部份分化为神经元及星形胶质细胞.三种分化细胞在加入GDNF移植组显著多于未加GDNF移植组(P均<0.05).移植后21 d光镜下脑病理显示,两个移植组的脑白质病理均获明显改善,尤其加人GDNF移植组的脑白质重度病变发生率较未加GDNF移植组下降了25.5%(P<0.01).移植后21 d的电镜显示,PVL组罕见髓鞘形成,两个移植组的髓鞘形成明显增加,尤其加入GDNF移植组的髓鞘形成明显多于未加GDNF移植组.结论 在外源性NSCs移植物内加入GDNF,可明显增强NSCs经脑室移植治疗PVL新生大鼠的移植疗效.

Transplant effect of neural stem cells combined with GDNF for the treatment of periventricular leukomalacia in neonatal rats

Objective To explore whether the glial cell line derived neurotrophic factor (GDNF) can enhance the effect of neural stem cells (NSCs) implanted into ventricle for the treatment of periventricular leukomalacia (PVL) in neonatal rats. Methods NSCs were prepared from E14 embryonic rat brain. Two-day-old neonatal rats were randomly divided into the PVL group, the PVL + NSCs group, the PVL + NSCs + GDNF group, the sham group, the sham + NSCs group, and the sham + NSCs + GDNF group. The intraventricular transpla...