免疫毒素192-IgG-saporin侧脑室注射建立阿尔茨海默病动物模型的实验研究

目的建立大鼠阿尔茨海默病(Alzheimer′sdisease,AD)动物模型,并观察其学习记忆能力及基底前脑胆碱能神经元改变。方法采用SD大鼠侧脑室注射192-IgG-saporin(2.5μg/5μl),21d后行Y迷宫检测,28d后处死大鼠,免疫组化观察基底前脑神经生长因子受体(NGFR)阳性神经元细胞数的变化。结果Y迷宫检测显示模型组大鼠的学习次数、记忆能力(107.38±9.34、3.75±0.71)较正常组明显下降(P<0.01)。免疫组化显示模型组损伤侧在内侧隔核(MS)和斜角带垂直支(VDB)的NGFR阳性神经元细胞数(7.50±1.77、15.00±2.27)与正常组对应侧比较分别减少81.96%和84.23%(P<0.01),MS和VDB的NGFR阳性神经元面积和周长降低(P<0.05),灰度值升高(P<0.05)。结论免疫毒素192-IgG-saporin侧脑室注射可以模拟AD行为学改变和部分病理学特征。

The experimental study on an animal model of Alzheimer's disease by intraventricular injection of the immunotoxin 192-IgG-saporin

ObjectiveTo establish an animal model of Alzheimer's disease in rats and to observe the alteration of learning and memory abilities of the animals and the changes of cholinergic neurons in the basal forebrain. Methods192-IgG-saporin (2.5 μg) was injected into the later ventricle of SD rats. After three weeks, learning and memory abilities were tested by Y-maze. After four weeks from the surgery, all the rats were sacrificed and the number of cholinergic neurons in the basal forebrain was counted through immunohistochemical method. ResultsY-maze test showed the abilities of learning and memory in the model groups (107.38±9.34, 3.75±0.71) were apparently decreased, in comparision with the normal groups, P<0.01. Immunohistochemistry showed the number of cholinergic neurons in basal forebrain was decreased by 81.96%, 84.23% respectively in medial septum (MS) and vertical diagonal branch (VDB). Significant difference was found between the model groups and the normal groups (P<0.01). The area and perimeter of neuron growth factor receptor (NGFR) positive neuron in MS/VDB of the model groups were significantly decreased (P<0.05). The gray walue in MS/VDB of the model groups were strikingly advanced (P<0.05). ConclusionThe intraventricular injection of the immunotoxin 192-IgG-saporin can simulate the alteration of the praxiology and pathological characteristics of AD partly.