高脂血症与Aβ的协同作用促进引发阿尔茨海默症

发布时间：2018-05-30 11:57

本文选题：高脂血症 + Aβ　；参考：《中国药理学通报》2017年04期

【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Aβ_(25-35)、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Aβ_(25-35)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,Aβ_(25-35)组、D-gal+Aβ_(25-35)组以及D-gal+Aβ_(25-35)+HLD组大鼠在目标象限停留时间明显减少(P0.01)、穿越平台的次数也减少(P0.01),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,Aβ_(25-35)组、D-gal+Aβ_(25-35)组以及D-gal+Aβ_(25-35)+HLD组海马神经元凋亡率明显增多(P0.01);与Aβ_(25-35)组相比,D-gal+Aβ_(25-35)组神经元凋亡率无明显变化,但D-gal+Aβ_(25-35)+HLD组神经元凋亡率明显增加(P0.01);与Dgal+Aβ_(25-35)组相比,D-gal+Aβ_(25-35)+HLD组神经元凋亡率明显增多(P0.01)。Western blot中,与sham组、Aβ_(25-35)组、Dgal组、HLD组、D-gal+Aβ_(25-35)组以及D-gal+HLD组相比,Dgal+Aβ_(25-35)+HLD组大鼠tau蛋白Thr181位点的磷酸化明显增加(P0.01)。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。
[Abstract]:Objective to investigate the interaction and pathological changes between hyperlipidemia and amyloid-beta peptides-A 尾 during Alzheimer's disease (AD) in aging rats. Methods 70 Sprague-Dawley rats were randomly divided into 7 groups according to their body weight. The other rats were given subcutaneous injection of D-galactose-D-galactosine for 6 weeks to make aging model, and hyperlipidemia model was established by hyperlipidemia. The compound model of hyperlipidemia accompanied with AD in aging stage was established by injecting condensed matter A 尾 (25-35) into bilateral hippocampal CA1 region. The effects of hyperlipidemia on learning and memory, hippocampal neuronal apoptosis and the changes of specific sites of tau protein hyperphosphorylation in aged AD rats were studied by Morris water maze, Nissl staining Western blot and immunohistochemical staining. Results in the Morris water maze experiment, compared with the sham group, the D-gal A 尾 -tip25-35) group and the D-gal A 尾 25-35) HLD group significantly decreased the duration of stay in the target quadrant and the number of crossing the platform, but there was no significant difference between the D-gal HLD group and the sham group in D-gal group. In Nissl's staining, the apoptotic rate of hippocampal neurons in the D-gal A 尾 group and D-gal A 尾 -35) group was significantly higher than that in the sham group, and the apoptotic rate of the hippocampal neurons in the HLD group was significantly higher than that in the A 尾 group, and there was no significant change in the apoptosis rate in the D-gal A 尾 tip-35 group compared with the group A 尾 -35). However, the apoptosis rate of neurons in the D-gal A 尾 25-35) HLD group was significantly higher than that in the Dgal A 尾 25-35) group, and that in the D-gal A 尾 25-35) HLD group was significantly higher than that in the Dgal A 尾 25-35) group. The phosphorylation of tau protein Thr181 site in Dgal group and D-gal HLD group was significantly higher than that in Dgal group and D-gal HLD group. The phosphorylation of tau protein Thr181 site in HLD group was significantly higher than that in HLD group. Conclusion Hyperlipidemia has no effect on learning and memory ability and antioxidant ability of aged rats, hyperlipidemia can synergize with A 尾, aggravate the damage of A 尾 to neurons, and promote the hyperphosphorylation of Thr181 site of tau protein. It is a risk factor for AD.
【作者单位】：山东中医药大学中医学院;山西中医学院基础医学院;中国医学科学院药物研究所&神经科学中心;湖南中医药大学药学院;
【基金】：国家自然科学基金资助项目(No 81573853,81273629) 中国医学科学院医学与健康科技创新工程重大协同创新项目(创新团队项目)(No 2016I2M1004) 山西省回国留学人员科研资助项目(No 2013-134) 湖南省重点研发计划项目(No 2015SK2029-1)
【分类号】：R749.16;R589.2

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