侧脑室注射192-IgG-saporin致痴呆动物模型的实验研究

THE STUDY ON DEMENTIA MODELS INDUCED BY INTRACEREBROVENTRICULAR INFUSION OF 192-IgG-SAPORIN

建立老年性痴呆模型大鼠,并观察其学习记忆能力及基底前脑胆碱能神经元数目的变化。在成年SD大鼠左侧侧脑室注射免疫毒素192-IgG-saporin(2.5μg/5μl),3周后行Y迷宫检测其学习和记忆能力;4周后处死大鼠,采用免疫组化结合图像分析技术观察各组大鼠基底前脑ChAT阳性神经元数目的变化。结果显示:模型组大鼠的学习记忆能力与正常组相比明显下降(P<0.01);模型组基底前脑的内侧隔核(MS)和斜角带垂直部(VDB)胆碱能神经元数目分别减少至正常组的9.70%和14.09%,与正常组相比均明显下降(P<0.01);学习、记忆能力与基底前脑胆碱能神经元数目密切相关。上述结果表明应用192-IgG-saporin免疫毒素能成功建立AD大鼠动物模型,该模型可用于抗痴呆药物的筛选及药效的评价。

To establish a rat model of Alzheimer＇s disease and observe the alteration of learning and memory ability, and the change of the number of cholinergic neurons in basal forebrain of the model rats, 192-IgG-saporin （2.5 μg/5 μl） was unilaterally injected into the lateral ventricle of SD rats. After three weeks, learning and memory abilities were measured by Y-maze test. Four weeks after surgery, all rats were sacrificed and the change of the number of cholinergic neurons in basal forebrain was analyzed by using immunohistochemical method combined with technique of micromeasure and image analysis. The results showed that the abilities of learning and memory of the model group were apparently decreased in comparison with the normal groups （ P 〈 0.01 ） and the number of cholinergic neurons in the model group were decreased to 9.70% and 14.09% of the normal group respectively in medial septum （ MS ） and vertical diagonal branch （VDB） , and significant difference was found between the model group and normal control group （P 〈 0.01 ） . The abilities of learning and memory were closely related with the number of cholinergic neurons in the basal forebrain. The present results suggest that immunotoxin 192-IgG-saporin can perfectly establish an animal model of Alzheimer＇s disease in rats, which can be used to screen the anti-dementia drugs and evaluate drug effect.