姜黄素对APP/PS1双转基因小鼠脑葡萄糖转运子表达的影响  

Effects of curcumin on expression of hippocampal glucose transporter of APP/PS1 double transgenic mice

作　　者：党惠子[1] 王虹[2] 李瑞晟[3] 任映[1] 杨金铎[1] 王蓬文[1] 

机构地区：[1]北京中医药大学东直门医院中医内科学教育部重点实验室和北京市重点实验室,100700 [2]北京美中宜和妇儿医院妇产科 [3]新疆医科大学第二附属医院老年病老年干部科

出　　处：《中国糖尿病杂志》2014年第1期68-72,共5页Chinese Journal of Diabetes

基　　金：国家自然科学基金面上资助项目(81073076);高等学校学科创新引智基地(111计划)教育部和国家外国专家局资助项目(B08006)

摘　　要：目的采用Morris水迷宫检测小鼠空间学习记忆和记忆保持能力,评价姜黄素对APP/PS1双转基因小鼠认知功能的影响,并观察姜黄素对APP/PS1双转基因小鼠以及海马葡萄糖转运子1(GLUT1)和GLUT3表达的影响,从脑能量代谢的角度探讨姜黄素神经保护作用的机制。方法将3月龄APP/PS1双转基因小鼠随机分为模型(APP/PS1+VEH)组,罗格列酮(APP/PS1+RSG)组,姜黄素大(APP/PS1+curcumin-H)、中(APP/PS1+curcumin-M)、小剂量(APP/PS1+curcumin-L)组。灌胃3个月后,应用免疫组织化学和Western blot方法进行检测。结果 Morris水迷宫撤台实验中,与正常对照(NC)组比较,APP/PS1+VEH组穿越平台次数减少,且目标象限停留时间缩短(P<0.01);与APP/PS1+VEH组相比,APP/PS1+curcumin-M组穿越平台次数增加(P<0.01)。免疫组织化学染色,与APP/PS1+VEH组相比,APP/PS1+curcumin-H、APP/PS1+curcumin-M组海马CA1区GLUT1阳性细胞增加(P<0.05);APP/PS1+curcumin-M组GLUT3阳性细胞计数明显增加(P<0.01),APP/PS1+curcumin-H组GLUT3阳性细胞增加(P<0.05)。Western blot结果与免疫组织化学结果基本一致。结论姜黄素可改善APP/PS1双转基因小鼠的空间学习记忆和记忆保持能力,影响脑葡萄糖代谢有关的GLUT1和GLUT3蛋白的表达而发挥神经保护作用。Objective The spatial learning, memory and memory retention ability in mice were assessed by Morris water maze, for evaluating the therapeutic effects of curcumin on cognitive function of APP/PS1 double transgenic （DTG） mice, and observing the effects of curcumin on the expression of hippocampal glucose transporter 1 （GLUT1）and GLUT3 and investigating the mechanism of curcumin neuroprotection from the perspective of brain energy metabolism. Methods 3-month old APP/PS1 DTG mice were randomly divided into model group, positive control rosiglitazone group and eurcumin group of large,medium and small dose. After 3 months of gavage,immunohistochemistry and Western blot methods were applied to detect learning and memory ability of these mice. Results Through Morris water maze, the platform crossing frequency were decreased in APP/PS1 DTG mice as compared with normal control,and the time staiing in target quadrant was shorten（all P〈0. 01）, the platform crossing frequency of APP/PS1＋curcumin-M group was increased as compared with APP/PS1 DTG mice. As compared with APP/ PS1 DTG mice＋VEH group, immunohistochemistry showed that GLUT1 positive ceils at hippocampus CA1 area in the APP/PS1 q-curcumin-H and the APP/PS1＋curcumin-M group were significantly increased（P〈0.05）, GLUT3 positive cells count was significantly increased in hippocampus CA1 area were markedly increased in the APP/PS1＋ cureumin-M group, and were significantly increased in the APP/PS1＋curcumiwH group （P〈 0.05）. The results of Western blot and immunohistochemistry were basically consistent. Conclusion Curcumin could improve the spatial learning memory and memory retention capacity of APP/PS1 double transgenic mice and affect the expression of cerebral glucose metabolism-related proteins such as GLUT1 and GLUT3 protein to protect the nerve.

关 键 词：姜黄素 APP PS1双转基因小鼠 葡萄糖转运子1 葡萄糖转运子3 

分 类 号：R285.5[医药卫生—中药学]