神经生长因子偶联物对老年性痴呆动物模型的保护作用

The Effect of Nerve Growth Factor -Transferrin Conjugate on the Alzheimer's Disease Rats

目的 探讨神经生长因子偶联物 (NGF -Tf)对老年性痴呆 (AD)大鼠的影响 .方法 以手术切断大鼠双侧隔 -海马胆碱能通路的方法建立AD动物模型 ,每天从大鼠尾静脉注射NGF -Tf .通过水迷路试验观察大鼠的记忆和方向辨别能力 ;对海马和隔区行神经组织学检查 ;应用酶组织化学技术显示相应区域的ChAT ,采用计算机病理图像分析系统测定酶活性以判断其胆碱能功能状态 .结果 水迷路试验中 ,NGF -Tf组在 10s内抵达平台的正确反应平均数提高 (p <0 .0 5 ) .光镜下 ,NGF -Tf组隔区仅见轻微萎缩性改变 ,而模型组隔区萎缩性改变较明显 ,表现为神经元数目明显减少 ,细胞轮廓不清 ,有胶质细胞增生 ;正常对照组、NGF -Tf组和模型组的海马区未见明显病理性改变 .ChAT染色统计结果显示 ,正常对照组、NGF -Tf组大鼠的海马区及隔区IOD值与模型组比较 ,均有显著性差异 (p <0 .0 1) .结论 NGF -Tf能穿透血脑屏障 ,有效防止模拟AD病变的大鼠的基底前脑胆碱能神经元的变性和死亡 ,改善其记忆和方向辨别能力 。

Objective Study the effect of Nerve growth factor-transferrin conjugate(NGF-Tf) on the Alzheimer's disease(AD) rats. Methods NGF-Tf was daily injected into Wistar rats with bilateral lesions of the cholinergic septo-hippocampal pathway. We observed the rats' abilities of studing and discriminating the direction by using water maze test. Septum and hippocampus were conducted in morphological examination with light microscope. Choline acetyltransferase(ChAT) activities of septum and hippocampus were also shown by using enzyme histochemistry technique, and were analysed with computer image analysis system. Results In water maze test, the average right reaction number arriving terrace of NGF-Tf group within 10 seconds was higher than that of model group (p<0.05). Under microscope, Septum of NGF-Tf group had a light withered change, but the nerve cells of model group in septum were markedly reduced, their outlines were blurred, and there were neuroglial cells proliferated; hippocampuses of normal control group and model group and NGF-Tf group had no obvious pathological change. The statistics results also showed the integrating optical densities(IOD) of ChAT of NGF-Tf group and normal group were higher than that of model group (p<0.01). Conclusions It is demonstrated that NGF-Tf can pass through Blood-brain barrier(BBB), effectively prevent the degeneration and death of cholinergic nerve cells in the AD rat basal forebrain, improve AD rats' abilities of study and memory, and promote the function of cholinergic nerve cells to be resumed.