BDNF、NGF对AD模型鼠脑移植区一氧化氮合酶阳性神经元发育生长的影响

用使君子酸（ＱＡ）损毁ＳＤ 大鼠左侧Ｍ ｅｙｎｅｒｔ基底大细胞核，制成老年性痴呆症（ＡＤ）模型。将同种鼠胚基底前脑制成的细胞悬液不加神经营养因子和分别加入脑源性神经营养因子（ＢＤＮＦ）、神经生长因子（ＮＧＦ）及ＢＤＮＦ＋ ＮＧＦ者植入ＡＤ 模型鼠额、顶叶皮质，隔日通过脑室灌注人工脑脊液和相应神经营养因子共７ 次。移植后４ 个月，取脑切片作Ｎｉｓｓｌ染色、ＮＡＤＰＨ ｄ和ＮＡＤＰＨ ｄ＋ ＡＣｈＥ 组化染色，计数移植区中ＮＯＳ阳性神经元数及其纤维在１６９００ μｍ ２ 网格中的交点数，并用ＭＩＡＳ ３００ 计算机图像分析系统对移植区中ＮＯＳ阳性神经元的细胞面积进行处理。结果显示：给予神经营养因子的动物，移植区中的ＮＯＳ阳性神经元数、ＮＯＳ阳性纤维交点数和ＮＯＳ阳性神经元的细胞面积等形态学指标均较不给予神经营养因子的对照组为佳，而在应用神经营养因子的各组中又以ＢＤＮＦ＋ ＮＧＦ组为优，提示ＢＤＮＦ、ＮＧＦ能促进移植区中ＮＯＳ阳性神经元的发育生长，ＢＤＮＦ与ＮＧＦ联合使用可发挥协同作用。本文对ＢＤＮＦ和ＮＧＦ促进移植区中ＮＯＳ阳性神经元发育生长的机制进行了探讨。

EFFECTS OF BDNF AND NGF ON THE DEVELOPMENT AND GROWTH OF NITRIC OXIDE SYNTHASE POSITIVE NEURONS IN BRAIN GRAFTS OF AD MODEL RATS

Alzheimer's disease (AD) model rats were obtained by destroying the left nucleus basalis of Meynert with quisqualic acid (QA). The cell suspensions were prepared from the fetal basal forebrain of the same species rat. The suspensions without or with addition of BDNF, NGF and BDNF+NGF were respectively implanted into the frontal and parietal cortex of AD model rats. The artificial cerebrospinal fluid and the corresponding neurotrophic factors were injected into the cerebral ventricle every two days for seven times. Four months later, the rat brain were sliced. The series slices of the brains were stained with Nissl stain, NADPH d and NADPH d+AChE histochemical methods. The number of NOS positive neurons and its fibers crossing points in 16900 μm 2 grid were counted. And the cell area of NOS positive neurons in grafts were treated with MIAS 300 computer image analysis system. The results showed that in the animals using neurotrophic factors the morphological data, such as the number of NOS positive neurons, NOS positive fibers crossing points and the cell area of NOS positive neurons in the grafts were superior to those of control animals containing no neurotrophic factors and the results of BDNF+NGF group were better than other groups adding BDNF or NGF, suggesting that BDNF and NGF can promote the development of NOS positive neurons in the grafts and the combined use of BDNF and NGF may play a kind of synergic role. The mechanism of BDNF and NGF promoting the development and growth of NOS positive neurons in brain grafts were discussed. (Figures 1～6 on plate 31)