摘要
目的初探雷帕霉素(RAPA)对APP/PS1转基因小鼠学习记忆及海马β淀粉样蛋白1-42(Aβ_(1-42))表达的影响。方法 APP/PS1转基因小鼠雌雄各半,随机分为模型组、RAPA低剂量组、RAPA中剂量组和RAPA高剂量组,野生型C57BL/6小鼠作为对照组,每组10只。RAPA各组小鼠每天分别灌胃1.12、2.24和4.48 mg/kg的RAPA,连续4周。跳台和Morris水迷宫实验检测小鼠学习记忆能力,Western Blot检测海马神经元Aβ_(1-42)、磷酸化蛋白激酶B(p-PKB)和磷酸化哺乳动物雷帕霉素靶蛋白(p-m TOR)的表达。结果模型组较对照组小鼠跳台学习成绩下降、潜伏期缩短、错误次数增加;Morris水迷宫逃避潜伏期延长、目标象限停留时间缩短、穿环次数减少;海马Aβ_(1-42)和p-m TOR表达增多、p-PKB表达减少(P<0.05)。与模型组比较,RAPA各组小鼠跳台学习成绩提高、潜伏期延长、错误次数减少;Morris水迷宫逃避潜伏期缩短、目的象限停留时间延长、穿环次数增多;海马Aβ_(1-42)和p-m TOR表达减少、p-PKB表达增多(P﹤0.05)。RAPA各组组间比较,各指标均无统计学差异(P>0.05)。结论 RAPA可降低海马Aβ_(1-42)的表达,对APP/PS1转基因小鼠学习记忆具有改善作用,其机制可能与调节PKB/m TOR信号通路活性有关。
Objective Explore the effects of Rapamycin（RAPA） on the learning and memory and the expression of Aβ（1-42） in hippocampus of APP/PS1 transgenic mice. Methods APP/PS1 transgenic mice were randomly di- vided into the model group and RAPA groups（low dose RAPA,middle dose RAPA, and high dose tlAPA） , wild - type C57BL/6 mice were used as the control group with ten mice in each group and half male and half female. RAPA groups were given 1.12,2.24,4.48 mg/kg RAPA for four weeks by garage. Step down test and Morris water maze test were used to investigate the learning and memory ability. The expression of Aβ（1-42）（ beta - amy- loid peptides 1 - 42） of hippocampal neurons, p - PKB （ protein kinase B with phosphorylation） and p - roTOR （mammalian target of rapamycin with phospho^71ation ）were detected by Western blot. Results Compared the model group with the control group, the achievement of step down test was decreased, latent period was shorter, the number of mistakes was inereased;the escape latency was longer, the target quadrant time were shorter and the number of quadrant entries were less, the expression of Aβ（1-42）in hippocampus and p - roTOR were increased while the expression of p - PKB was decreased （P 〈 0.05 ）. Compared RAPA groups with the model group, the result of step down test was increased,latent period was longer, the number of mistakes was decreased ; the escapelatency was shorter,the target quadrant time were longer and the number of quadrant entries were more, the ex- pression of Aβ（1-42） in hippocampus and p - mTOR were decreased while the expression of p - PKB was increased （P 〈 0.05 ）. Comparisons among RAPA groups showed that there were no statistical differences in each index（P 〉0.05 ）. Conclusion RAPA may decrease the expression of Aβ（1-42）in hippocampus and improve the learning and memory ability of APP/PS1 transgenic mice, which may be related to the regulation of PKB/mTOR signaling pathway.
出处
《遵义医学院学报》
2017年第3期254-258,共5页
Journal of Zunyi Medical University
基金
贵州省科技厅基金资助项目(NO:黔科合LKZ字[2012]17)
贵州省科技厅基金资助项目(NO:黔科合LKZ字[2011]43)
贵州省教育厅自然科学研究项目(NO:黔教科[2009]0108)
