Neurturin和NGF联合应用对AD模型鼠基底前脑NGFR阳性神经元的保护作用

EFFECTS OF COMBINED NEURTURIN AND NGF ON THE CHOLINERGIC NEURONS OF BASAL FOREBRAIN OF AD MODEL RAT

本研究目的是探讨neurturin和神经生长因子(NGF)联合应用对穹窿-海马伞(FF)切断后基底前脑胆碱能神经元的保护作用。将这两种因子联合注射到FF切断的大鼠侧脑室,注射一个月后,取脑进行免疫组化结合图像分析方法对内侧隔核(MS)和斜角带核垂直支(VDB)的神经生长因子受体(NGFR)阳性神经元存活情况进行比较分析。结果表明:FF切断一个月后,损伤组损伤侧MS和VDB的NGFR阳性神经元大量减少(分别减少64.8％和51.4％),MS和VDB的NGFR阳性细胞的面积和周长显著降低(P<0.01),OD值显著增高(P<0.01);NGF组损伤侧NGFR阳性神经元受到保护,NGFR阳性经元数显著高于损伤组损伤侧(P<0.01);联合组损伤侧NGFR阳性神经元也受到保护(MS和VDB细胞数分别只下降7.3％和15.4％),与损伤组损伤侧比较NGFR阳性细胞数增加了57.4％和36.0％(P<0.01),也明显高于NGF组(P<0.05);细胞形态学参数明显改善(P<0.05),细胞膜受体含量显著提高(P<0.05)。结果提示,neurturin和NGF联合应用和NGF单独应用均能不同程度地保护基底前脑胆碱能神经元,联合应用效果更佳。

To investigate the effects of combined neurturin and NGF on the cholinergic neurons of basal forebrain, AD model rats with left fimbria-fornix lesions received continuous infusion of neurturin and NGF into the lateral ventricle. One month after lesion the rats were killed and the brain sections including basal forebrain were cut coronally on a freezing microtome and processed by immunohistochemistry staining with antibodies against NGFR, combining with technique of micromeasure and image analysis. The unilateral fimbria-fornix(FF) was transected to stimulate the impairment of cholinergic neurons of AD by the lesion of the pathway of septohippocampus. The results showed that after FF lesion, the percentages of NGF-R positive neurons at the lesion side to the intact side of MS and VDB were 35. 2% and 48. 6%. The morphological data of the cells in MS/VDB were all significantly decreased (P<0. 01). After 30 days following a continuous infusion of NGF or/and NRTN in the lateral ventricle , NGF not only preserved the total number of NGFR positive neurons, but also maintained at normal levels in the size and shape of the saved neurons. After combinational therapy, the percentages of NGFR positive neurons at the lesion side to the intact side of MS and VDB were 92. 7% and 84. 6% , which were significantly higher than that in the lesion group(35. 2% and 48. 6%, P<0. 01 respectively), also significantly higher than that in the NGF group (78. 9% and 71%, P<0. 05 respectively). The effects of combinational therapy on the number and morphology of NGFR positive neurons at MS and VDB was superior to thoseof using only NGF. The results suggest that the injured cholinergic neurons can be protected in different extent after treatment with combination of neurturin and NGF.