神经干细胞与脑源性神经营养因子联合治疗对老年性痴呆鼠基底前脑一氧化氮合酶阳性神经元的影响

EFFECTS OF COMBINED NEURAL STEM CELLS AND BDNF ON NOS-POSITIVE NEURONS OF BASAL FOREBRAIN OF AD RAT

目的探讨神经干细胞(NSCs)与脑源性神经营养因子(BDNF)联合应用对老年性痴呆鼠基底前脑一氧化氮合酶(NOS)阳性神经元的影响。方法切断成年SD大鼠左侧穹窿海马伞(FF),基底前脑行神经干细胞移植,同时持续侧脑室注射BDNF,4周后行组织化学染色结合图像分析技术观察各组大鼠基底前脑NOS阳性神经元数量和形态学参数的变化。结果损伤后1个月,损伤侧基底前脑内侧隔核(MS)和斜角带垂直支(VDB)内可观察到NOS阳性神经元明显减少,分别为正常组的35.5%和55.8%,(与正常组相比P<0.01);移植组NOS阳性神经元数恢复到正常组的74.7%和95.7%,(与损伤组相比P<0.01);联合组NOS阳性神经元数达到正常组的115.2%和151.3%,(与移植组相比P<0.05及P<0.01)。细胞形态学参数提示,移植组NOS阳性神经元中含部分中等大小的未成熟细胞;联合组中该中等大小的细胞更多。结论神经干细胞移植与BDNF联合治疗,对AD模型鼠基底前脑MS、VDB的NOS阳性神经元有明显的补充和保护作用,并且联合治疗效果比单纯神经干细胞移植效果更佳。

Objective To investigate the effects of combined neural stem cells （NSCs） and brain-derived neurotrophic factor （BDNF） on NOS-positive neurons of basal forebrain of rats with Alzheimer disease （AD）. Methods Adult SD rats with left fimbfia-fomix （FF） transection received neural stem ceils transplanted in the basal forehraln. Then BDNF was continuous injected into lateral ventricle. After 4 weeks, morphologic data and percentages of NOS-positive neurons were measured in basal forebrain by using histoehemieal method combined with technique of and image analysis. Results About 1 month after FF lesion, 35.5% and 55.8% of NOS-positive neurons were survived in medial septum （MS） and vertical diagonal band （VDB） of the lesion side of basal forebrain, （P 〈 0.01, compared with the normal control group）. After the transplantation of NSCs, 74.7%/95.7% of NOS-positive neurons were survived in MS/VDB, （P 〈 0.01 as compared with the lesion group）. After combinative therapy, about 115.2% and 151.3% of NOS-positive neurons were survived in MS and VDB （P 〈 0.05/P 〈 0.01, compared with the grafting group）, respectively. The morphologic data of NOS-positive neurons indicated that there were some premature cells among them in grafting group and more in combinafing group. Conclusion The results suggest that the NOS-positive neurons in MS and VDB of basal forebrain of AD rats could be improved and protected after treatment with combination of neural stem cells and BDNF which is superior to neural stem cells grafting alone.