NGF／GDNF基因修饰神经干细胞植入AD模型鼠脑内的存活、分化及表达

目的 观察NGF／GDNF基因修饰神经干细胞（NGF－NSC和GDNF－NSC）在AD模型鼠脑内的存活、分化及基因产物的表达。方法 将BrdU标记的NGF－NSC和GDNF－NSC单独和联合移植入穹窿海巴伞切断的大鼠侧脑室内。移植后3周，用免疫组织化学方法对脑切片进行BrdU、Nestin、GFAP、NF、NGF及GDNF单标或双标染色。结果 脑室内见到大量BrdU阳性细胞。部分移植细胞向脑实质迁移，在切口周围、穹窿海马伞、海马、胼胝体、隔区、室管膜下区及血管壁旁均可见到BrdU阳性细胞。在皮质和切口周围可见较多的BrdU＋GFAP双标细胞；在海马内可见较多的BrdU NF双标细胞；在脑室内，两者均可见到。在脑室、皮质和海马等处均检测出BrdU＋NGF和BrdU＋GDNF免疫双标阳性细胞。结论 NGF／GDFN基因修饰NSC能在宿主脑内较好地存活，并能分化成神经元和星形胶质细胞，而且能分别表达外源基因产物NGF和GDNF。

SURVIVAL,DIFFERENTIATION AND GENE EXPRESSION OF THE NEURAL STEM CELLS MODIFIED BY THE GENE OF NGF OR GDNF IN THE BRAIN OF AD RAT MODEL AFTER TRANSPLANTATION

Objective To investigate the survival,differentiation and gene expression of the neural stem cells(NSCs) modified by the gene of NGF or GDNF in the brain of AD rat model after transplantation. Methods The NGF or GDNF genetically modified NSCs labled with BrdU were implanted into the lateral cerebral ventricle of the AD rat model.The rats were killed three weeks after transplantation.The brains were cut and the sections were processed for single or double immunochemistry staining with antibodies against BrdU,Nestin,GFAP,NF,NGF and GDNF. Results BrdU|positive cells were found in the lateral cerebral ventricle.Some of them migrated into the parenchyma and located in the wound,fibria|fonix,hippocampus,corpus callosum,septum,subventricle zone and beside the blood vessels.Cells of doubled labeling with anti|BrdU and GFAP were more often seen in the cortex,whereas more cells with anti|BrdU and NF in the hippocampus,and both of them in the ventricle.Doubled labeling cells against BrdU and NGF,and against BrdU and GDNF were found in the ventricle and parenchyma.Conclusion The NGF or GDNF genetically modified NSCs can not only survive well,but also differentiate into neuron and astrocyte,and express the exogenous genes of NGF and GDNF in the host brain