中文摘要：

目的探讨高脂血症与β样淀粉蛋白（amyloid-beta peptides,Aβ）在衰老大鼠发生阿尔茨海默病（Alzheimer’s disease,AD）时的相互作用及病理变化。方法 70只♂SD大鼠按体重随机分为7组,除sham组及Aβ25-35、HLD组外,其余大鼠均给予皮下注射D-半乳糖（D-gal）6周,制备衰老模型;在此基础上给予高脂饲料,制备高脂血症模型,以及双侧海马CA1区定位注射凝聚态Aβ25-35构建衰老期高脂血症伴发AD的复合模型。采用Morris水迷宫、尼氏染色、Western blot、免疫组织化学染色等方法,观察高脂血症对老年AD大鼠学习记忆、海马神经元凋亡以及tau蛋白过度磷酸化特异性位点改变的影响。结果在Morris水迷宫实验中,与sham组相比,Aβ25-35组、D-gal＋Aβ25-35组以及D-gal＋Aβ25-35＋HLD组大鼠在目标象限停留时间明显减少（P〈0.01）、穿越平台的次数也减少（P〈0.01）,而D-gal组、HLD组、D-gal＋HLD组与sham组相比差异无显著性。尼氏染色中,与sham组相比,Aβ25-35组、D-gal＋Aβ25-35组以及D-gal＋Aβ25-35＋HLD组海马神经元凋亡率明显增多（P〈0.01）;与Aβ25-35组相比,D-gal＋Aβ25-35组神经元凋亡率无明显变化,但D-gal＋Aβ25-35＋HLD组神经元凋亡率明显增加（P〈0.01）;与Dgal＋Aβ25-35组相比,D-gal＋Aβ25-35＋HLD组神经元凋亡率明显增多（P〈0.01）。Western blot中,与sham组、Aβ25-35组、Dgal组、HLD组、D-gal＋Aβ25-35组以及D-gal＋HLD组相比,Dgal＋Aβ25-35＋HLD组大鼠tau蛋白Thr181位点的磷酸化明显增加（P〈0.01）。结论高脂血症对老年大鼠的学习记忆能力以及抗氧化能力无明显影响;高脂血症可与Aβ协同作用,加重Aβ对神经元的损伤,并促进tau蛋白Thr181位点的过度磷酸化,是引发AD的危险因素。

英文摘要：

Aim To research the synergistic effect of hyperlipoproteinemia and Aβ in the processing ofAlzheimer’s disease.Methods Seventy SD rats were randomly divided into seven groups,and dealt with D-gal（ hypodermic injection）,hyperlipemia diet,microinjection into both side of CA1 section in hippocampus,independently.Morris water maze（ MWM） test was used to evaluate the spatial memory impairments.Tau and tau（pThr181） pathology in the hippocampus were detected using Western blot and immunohistochemistry.Nissl’s staining was used to detect cell apoptosis.Results Aβ25-35-treated rats showed significant impairments of spatial memory in MWM test,especiallyin the group of D-gal ＋ Aβ25-35＋ HLD（ P 〈 0.01）.Furthermore,these rats treated with Aβ25-35,D-gal,and hyperlipemia diet,exhibited significantly increased phosphorylation of tau,particularly in the Thr181 site.Conclusion Hyperlipoproteinemia is the risk factor for older person,which could strengthen the toxic effect of Aβ,and promote phosphorylation of tau.