摘要
目的研究二甲双胍对侧脑室注射链脲佐菌素(STZ)所诱导的阿尔采末病(Alzheimers disease,AD)动物模型的保护作用。方法选用Morris水迷宫试验评估二甲双胍对STZ侧脑室注射诱导的AD动物模型的学习记忆能力的影响;采用蛋白免疫印迹法分析二甲双胍对AD动物模型脑内细胞骨架蛋白神经丝蛋白及Tau蛋白磷酸化的表达水平的影响。结果二甲双胍对链脲佐菌素侧脑室注射所诱导的AD模型小鼠的学习记忆能力有明显的改善作用。①Morris水迷宫:定位航行试验中,STZ组平均逃避潜伏期和路径长度较对照组明显增加,二甲双胍治疗组平均逃避潜伏期和路径长度较STZ组明显减少;空间探索试验中,STZ组穿越隐匿平台次数较对照组明显减少,二甲双胍治疗组穿越隐匿平台次数较STZ组明显增加(P均<0.05)。②Westernblot:与对照组相比,STZ组细胞骨架神经丝和tau蛋白的磷酸化较正常组表达明显增多,二甲双胍治疗组细胞骨架神经丝和tau蛋白的磷酸化较STZ组明显减少(P均<0.05)。结论二甲双胍可以改善小鼠阿尔采末病(AD)样的学习记忆能力的减退和早期细胞骨架的病理学改变。
Aim To explore the protective effect of metformin on AD animal models induced by STZ. Methods Streptozotocin （STZ） was used to induce AD model;metformin was administered through a gas- tric tube every day,whereas the control and STZ groups were given the same volume water. Morris water maze test was employed to assess the protective function of metformin on AD animal model; the hippocampus of mice was isolated for the determination of protein con- centration using Western blot; the protein samples were immunoblotted with antibodies to detect the phospho- rylation of neurofilament and tau. Results There was significant improvement on the learning and memory a- bilities of those STZ-induced mice treated by metform- in. ①Morris water maze：the swimming time and dis- tance to find the platform in the located navigation test increased significantly in mice treated with STZ corn-pared to the control; the number through the hidden platform in spatial probe test was reduced obviously in STZ-treated mice compared to the control group （P 〈 0.05 ）. ②Analysis of Western blot ： the enhanced ex- pressions of phosphorylation of neurofilament and tau detected by SMI31 and site-specific tau antibodies were obvious in mouse brain treated with STZ compared to the control brain, displaying statistic difference. These changes were inhibited by metformin （14, 3 mg . kg-1）. Conclusion Metformin can suppress the im- pairment of Alzheimer＇s disease-like learning and mem- ory in mice induced by STZ and the AD-like early cy- toskeleton associated pathology.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2013年第6期871-876,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 30973156
81270422)
关键词
二甲双胍
阿尔采末病
链脲佐菌素
侧脑室注射
tau蛋白
神经丝
磷酸化
metformin
Alzheimer＇s disease
STZ
in- tracerebroventricular injection
tau protein
neurofila- ment
phosphorylation
作者简介
宋金芝（1987-），女，硕士，研究方向：阿尔采末病神经退行性疾病，Tel：022—83336830，E-mail：sjzhinx@163．com；
熊慧（1988-），女，硕士，为此文章的共同第一作者，E-mail：xionghui0305@yahoo．com．cn；
邓艳秋（1966-），女，博士，教授，硕士生导师，研究方向：老年神经退行性疾病，通讯作者，Tel：022-83336830，E-mail：dengyanqiu66@gmail．com
