京尼平苷酸对APP/PS1小鼠学习记忆能力及脑内淀粉样蛋白沉积的影响  

Effect of geniposidic acid on learning and memory abilities andβ-Amyloid aggregations in APP/PS1 Mice

作　　者：周张玖智 侯加卫 任盟乔 杨光 屈祖卫 胡艳丽 Zhou Zhangjiuzhi;Hou Jiawei;Ren Mengqiao;Yang Guang;Qu Zuwei;Hu Yanli(Department of Phamacy,Shihezi University/Key Laboratory of Xingjiang Phytomedicine Resources,Shihezi,Xinjiang 832000,China)

机构地区：[1]石河子大学药学院/新疆植物药资源利用教育部重点实验室

出　　处：《石河子大学学报（自然科学版）》2019年第3期382-388,共7页Journal of Shihezi University(Natural Science)

基　　金：国家自然科学基金项目(81660603);新疆兵团社会发展科技攻关与成果转化计划项目(2016AD001)

摘　　要：目的探讨京尼平苷酸(GPA)对阿尔茨海默病转基因小鼠学习记忆能力的影响及对脑内淀粉样蛋白沉积的作用及机制。方法APP/PS1转基因小鼠随机分为转基因组、GPA 25,50,75 mg/kg组及多奈哌齐组。C57BL/6小鼠为野生组。灌胃给药90 d后,通过Morris水迷宫实验评价痴呆小鼠的学习记忆能力。硫黄素-T染色检测小鼠脑组织内硫黄素-T阳性斑块的沉积。Western Blot法检测小鼠大脑皮层及海马内BACE及IDE蛋白水平。ELISA法检测小鼠大脑皮层及海马内IL-1β,IL-6,IL-4,TNF-α的水平。结果与野生组比较,转基因小鼠潜伏期明显增加,穿越平台次数明显减少(P<0.05),脑内Th-T斑块百分面积显著增多(P<0.01),IDE的蛋白水平显著降低且BACE的蛋白水平显著升高(P<0.01),IL-1β,IL-6和TNF-α含量均显著升高,IL-4含量显著降低(P<0.01)。与转基因小鼠比较,GPA 75 mg/kg剂量组转基因小鼠潜伏期明显缩短,穿越平台次数明显增多(P<0.05),GPA处理组小鼠脑内Th-T荧光面积百分比显著减少,IDE水平显著升高,BACE水平显著降低(P<0.01),GPA 50,75 mg/kg组小鼠脑内IL-1β,IL-6和TNF-α含量均显著降低(P<0.01或P<0.05),GPA 50 mg/kg明显升高小鼠皮层IL-4含量(P<0.05)。结论京尼平苷酸可通过影响Aβ的生成和降解两方面调控小鼠脑内Aβ水平,减轻转基因小鼠的神经炎症,发挥神经保护作用。Objective To investigate the effect and protect mechanisms of geniposidic acid on learning and memory defects and fibrillarβ-amyloid aggregations in APP/PS1 mice.Method Double transgenic APP/PS1 mice were randomly assigned into transgenic group,GPA 25 mg/kg group,GPA 50 mg/kg group,GPA 75 mg/kg group and donepezil group.C57BL/6J mice were used as wide-type group.Treatments were administered by oral gavage daily for ninety days.Morris water maze was tested to estimate the memory and spatial learning abilities of mice.Thioflavin-T(Th-T)staining were applied to assess fibrillarβ-amyloid aggregations in brain.The expression of BACE and IDE in the cortex and the hippocampus of mice were detected by Western blot.In order to quantify the expression of IL-1β,IL-6,IL-4,and TNF-α,ELISA kits were applied.Results Compared with wide-type mice,transgenic mice exhibited shorter escape latency and a reduced number of crossings(P<0.05),the percent area of Th-T-positive plaque in the cortex and hippocampus increased significantly(P<0.01),the protein expression of BACE increased and IDE decreased significantly(P<0.01),the expression of IL-1β,IL-6 and TNF-αreduced and IL-4 induced in brain significantly(P<0.01).Compared with transgenic mice,mice in 75 mg/kg GPA treatment groups had shortened escape latency and improved target searching capacity markedly(P<0.05).GPA could reduce the percent area of Th-T-positive plaque and the protein expression of BACE,increase the protein expression of IDE in brain of mice(P<0.01).50,75 mg/kg GPA could obviously increase the expression of IL-4 in the cortex(P<0.05)and decrease the expression of IL-1β,IL-6 and TNF-αsignificantly in brain(P<0.01or P<0.05).Conclusion GPA could effectively regulate the level of Aβin brain by effecting the production and degradation of Aβ,reducing neuroinflammation of brain,therefore protecting the neurons.

关 键 词：京尼平苷酸 APP/PS1转基因小鼠 Β-淀粉样蛋白 神经炎症 

分 类 号：R749.[医药卫生—神经病学与精神病学]