Dab2调控阿尔茨海默病小鼠模型海马内TGF-β1/SMADs信号传导并减轻其脑损伤  

Dab2 attenuates brain injury in APP/PS1 mice via targeting transforming growth factor-beta/SMAD signaling

作　　者：刘宝华[1] 邵胜敏[1] 白光辉[1] 邬伟[1] 林海燕[1] 商萍[1] 宋晓杰[2] 郑胜哲[3] 

机构地区：[1]温州医科大学附属第二医院康复中心,浙江温州325027 [2]吉林大学白求恩第一医院呼吸科,吉林长春130021 [3]延边大学附属医院神经内科,吉林延吉133000

出　　处：《中风与神经疾病杂志》2014年第6期514-517,共4页Journal of Apoplexy and Nervous Diseases

基　　金：浙江省医药卫生科技计划项目(2013RCA036)

摘　　要：目的研究Dab2蛋白对阿尔茨海默病疾病模型中TGF-β1/SMADs信号通路的调节作用以及其对阿尔茨海默病小鼠脑损伤的影响。方法 24只APP/PS1双转基因小鼠随机分为AD组、Vector组和Dab2组,每组8只,并将10只阴性对照小鼠作为对照组(Control)。对照组不做任何处理;饲养1个月后,AD组小鼠经双侧海马注射生理盐水,Dab2组小鼠双侧海马注射Dab2腺相关病毒质粒,Vector组小鼠双侧海马注射阴性对照质粒。所有小鼠于鼠龄9个月时进行行为学检测。10月龄时处死ELISA法检测脑组织中Aβ含量;Western blot检测海马中Dab2、TβRII和p-SMAD2/3的表达。结果 Dab2腺相关病毒质粒可在小鼠海马内高效表达Dab2。Dab2组小鼠海马组织中TβRII、p-SMAD2和p-SMAD3含量明显高于其阴性对照Vector组。Dab2组小鼠海马内Aβ含量明显低于Vector组,并且行为学评分明显高于Vector组小鼠。结论 Dab2过表达可通过上调TGF-β1/SMADs信号通路的传导,减轻阿尔茨海默病小鼠海马内Aβ的含量并改善其神经功能。Objective Study the role of Dab2 in regulation of TGF-beta 1/SMADs pathway and its influences on brain injuries in Alzheimer＇ s disease mice models. Methods 24 APP/PS1 transgenic mice were randomly divided into AD group,vector group and Dab2 group,8 in each group, and 10 negative control mice were used as control group. Mice of control group didn＇t receive any treatment,whereas the mice in AD, Dab2 and vector group were injected saline solution, Dab2 adeno-associated virus plasmid and negative control plasmid respectively in the bilateral hippocampus. All the mice undertook behavior test in the rat of age 9 months and were sacrificed in 10 months for ELISA and western blot analysis. Results Injection of Dab2 adeno-assoeiated virus plasmid could efficiently overexpress Dab2 in the hippocampus of mice. TβRII, p-SMAD2 and p-SMAD3 expression in hippocampal tissues of mice in Dab2 group were significantly higher than that of mice in Vector group. Besides, Aβ content in hippoeampus of mice in Dab2 group was obviously lower than that of vector group, whereas neurological score of mice in Dab2 group was significantly higher than that of the Vector group. Conclusion Dab2 could restore TGF-β1/SMADs pathway in the brain of APP/PS1 mice,and thus reduced Aβ content and improved the neurological function.

关 键 词：阿尔茨海默病 Dab2 转化生长因子p 淀粉样蛋白 神经元 

分 类 号：R742[医药卫生—神经病学与精神病学]