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載脂蛋白E基因敲除小鼠的行為學(xué)、血脂、軟腦膜微循環(huán)及腦組織病理形態(tài)學(xué)研究

發(fā)布時間:2018-06-12 02:30

  本文選題:載脂蛋白E基因敲除小鼠 + 阿爾茨海默病; 參考:《山東中醫(yī)藥大學(xué)》2005年碩士論文


【摘要】:目的:觀察載脂蛋白E基因敲除(ApoEKO)對小鼠行為學(xué)特征、血脂、軟腦膜微循環(huán)及腦組織病理形態(tài)學(xué)的影響。方法:取11、15~20、29~41周齡的ApoEKO小鼠,按周齡隨機(jī)分層分為青年模型組、成年模型組、老年模型組,取相同遺傳背景的11、29周齡正常C57BL/6J小鼠隨機(jī)分層分為青年對照組、老年對照組。分別對五組小鼠做跳臺試驗、自主運(yùn)動試驗和轉(zhuǎn)棒耐疲勞試驗。將前四組小鼠分別稱重、麻醉,采用顱窗法測定軟腦膜微循環(huán)血流量,取下腔靜脈血測定血脂,后快速取腦組織,觀察其光鏡及透射電鏡下病理形態(tài)學(xué)變化。結(jié)果:老年ApoEKO小鼠比同齡C57BL/6J小鼠學(xué)習(xí)記憶能力明顯下降,隨著年齡的遞增,ApoEKO小鼠學(xué)習(xí)記憶能力明顯下降;ApoE基因敲除對小鼠自主運(yùn)動無明顯影響;ApoEKO小鼠較同齡C57BL/6J小鼠中樞神經(jīng)系統(tǒng)和肢體協(xié)調(diào)能力明顯下降,且隨著年齡遞增,ApoEKO小鼠中樞神經(jīng)系統(tǒng)和肢體協(xié)調(diào)能力明顯下降;具有明顯的高脂血癥;軟腦膜微循環(huán)血流量顯著降低;腦組織病理形態(tài)學(xué)顯示軸突、樹突空泡變性,神經(jīng)原纖維纏結(jié),大量脂褐素,細(xì)胞外老年斑及微血管病變。結(jié)論:ApoEKO小鼠具有類似AD的行為學(xué)和病理學(xué)特征,具有高脂血癥,存在微循環(huán)障礙,可以作為一種接近遺傳因素?fù)p傷的AD的理想動物模型。
[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.
【學(xué)位授予單位】:山東中醫(yī)藥大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2005
【分類號】:R363;R361

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