载脂蛋白E基因敲除小鼠的行为学、血脂、软脑膜微循环及脑组织病理形态学研究

发布时间：2018-06-12 02:30

本文选题：载脂蛋白E基因敲除小鼠 + 阿尔茨海默病　；参考：《山东中医药大学》2005年硕士论文

【摘要】：目的:观察载脂蛋白E基因敲除(ApoEKO)对小鼠行为学特征、血脂、软脑膜微循环及脑组织病理形态学的影响。方法:取11、15～20、29～41周龄的ApoEKO小鼠,按周龄随机分层分为青年模型组、成年模型组、老年模型组,取相同遗传背景的11、29周龄正常C57BL/6J小鼠随机分层分为青年对照组、老年对照组。分别对五组小鼠做跳台试验、自主运动试验和转棒耐疲劳试验。将前四组小鼠分别称重、麻醉,采用颅窗法测定软脑膜微循环血流量,取下腔静脉血测定血脂,后快速取脑组织,观察其光镜及透射电镜下病理形态学变化。结果:老年ApoEKO小鼠比同龄C57BL/6J小鼠学习记忆能力明显下降,随着年龄的递增,ApoEKO小鼠学习记忆能力明显下降;ApoE基因敲除对小鼠自主运动无明显影响;ApoEKO小鼠较同龄C57BL/6J小鼠中枢神经系统和肢体协调能力明显下降,且随着年龄递增,ApoEKO小鼠中枢神经系统和肢体协调能力明显下降;具有明显的高脂血症;软脑膜微循环血流量显著降低;脑组织病理形态学显示轴突、树突空泡变性,神经原纤维缠结,大量脂褐素,细胞外老年斑及微血管病变。结论:ApoEKO小鼠具有类似AD的行为学和病理学特征,具有高脂血症,存在微循环障碍,可以作为一种接近遗传因素损伤的AD的理想动物模型。
[Abstract]:Aim: to observe the effects of apolipoprotein E knockout (ApoEKOA) on behavior, lipid, pial microcirculation and pathomorphology of brain tissue in mice. Methods: ApoEKO mice were randomly divided into youth model group, adult model group and senile model group. The normal C57BL / 6J mice with the same genetic background were randomly divided into young control group and elderly control group. Five groups of mice were tested by bench test, independent exercise test and rotation bar fatigue test. The first four groups of mice were weighed and anesthetized respectively. The microcirculation blood flow of pia meninges was measured by cranial window method, blood lipids were measured by blood from inferior vena cava, and the brain tissue was removed quickly. The pathological changes of the mice were observed under light microscope and transmission electron microscope. Results: the learning and memory ability of the aged ApoEKO mice was significantly lower than that of C57BL / 6J mice. The ability of learning and memory of ApoEKO mice decreased with the increase of age. The ability of central nervous system and limb coordination of ApoEKO mice was significantly lower than that of C57BL / 6J mice. In addition, the central nervous system and limb coordination ability of ApoEKO mice decreased with age, hyperlipidemia, decreased blood flow of pial microcirculation, histopathological changes of axon and dendritic vacuolar degeneration in ApoEKO mice, and hyperlipidemia were observed in ApoEKO mice. Neurofibrillary tangles, lipofuscin, extracellular senile plaques and microvascular lesions. Conclusion the behavior and pathology of the mice with the disease were similar to AD, and the mice had hyperlipidemia and microcirculation disorder, which could be used as an ideal animal model for AD with genetic damage.
【学位授予单位】：山东中医药大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R363;R361

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