Tau195-213肽段对阿尔茨海默病小鼠的免疫治疗作用及对Wnt/β-catenin通路相关因子表达的影响  

The effect of Tau195-213 peptide on the immune function of mice with Alzheimer′s disease and the expression of Wnt/β-catenin pathway related factors

作　　者：郭婉姝[1] 赵丽薇 杜丽娟 王一沙[3] 

机构地区：[1]辽宁省人民医院神经内三科,辽宁沈阳110033 [2]沈阳市第一人民医院神经内六科,辽宁沈阳110041 [3]沈阳医学院附属第二医院神经内一科,辽宁沈阳110002

出　　处：《解剖学研究》2017年第6期432-436,共5页Anatomy Research

基　　金：沈阳市卫生局科研项目计划(2013);辽宁省博士启动基金(2016011039-301)

摘　　要：目的探讨Tau195-213肽段对阿尔茨海默病小鼠(JNPL3小鼠)的免疫治疗作用,同时探究其对Wnt/β-catenin通路相关因子表达的影响。方法 JNPL3转基因小鼠30只,随机分为对照组(C组)、佐剂CFA-PT免疫组(CFA组)、tau195-213(P202/205)肽段免疫组(tau组),每组10只,3组小鼠每3周免疫1次,共进行5次免疫,每次免疫前取血清,ELISA检测tau抗体的滴度、检测IFN-γ和IL-4含量;Morris水迷宫检测小鼠的空间学习记忆功能;Western检测Wnt/β-catenin通路相关因子的表达。结果 tau195-213(P202/205)肽段免疫的小鼠血清中能够诱导出较高滴度的抗tau抗体,其免疫的小鼠体外脾细胞培养上清液中IL-4含量较高(P<0.05,VS C组和CFA组),IFN-γ含量未见明显差异(P>0.05)。Tau组小鼠平均逃避潜伏期低于CFA组和C组,而在目标象限花费的时间多于CFA组。Tau195-213(P202/205)肽段可以激活机体脑组织β-catenin、c-Myc蛋白的表达升高,降低GSK-3β蛋白表达。结论 Tau195-213(P202/205)肽段免疫JNPL3小鼠后,产生了具有治疗水平的抗体,并且该抗体可通过血脑屏障,其机制与Wnt/β-catenin通路相关。Objective To investigate the effect of Tau195-213 peptide on the immune function of mice with Alzheimer＇s disease （JNPL3 mice）, and to explore the effect of atenin peptide on the expression of Wnt/β-eatenin factors. Methods 30 JNPL3 transgenic mice, divided randomized into control group （group C） , adjuvant CFA-PT immune group （CFA group）, Tau195-213 （P202/205） peptide immunization group （tau group） , 10 rats in each group, three groups of mice were immunized once every 3 weeks, a total of 5 times before each vaccination immunization, the serum titer the detection of ELISA, detection of tau antibody of IFN- gamma and IL-4 content ; the function of learning and memory in Morris water maze test in mice ; Western to detect the expres- sion of Wnt/β-catenin and other related factors. Results Tau195-213 （P202/205） in mouse serum peptides can induce high titer of anti tau antibody, the immunized mice spleen cells were cultured in vitro with high content of IL-4 in the supernatant （P〈O.05, vs. C group and CFA group ）, IFN- gamma content showed no significant difference （P〉0.05）. The average escape latency of tau group was lower than that of CFA group and C group, but the time spent in the target quadrant was higher than that in group CFA. Tau195- 213 （P202/205） peptide can activate the expression of-catenin and c-Myc protein in the brain tissue, and decrease the expression of GSK-3 beta protein. Conclusions After immunization with tau195-213 （P202/205） peptide, JNPL3 nfice produced antibodies with therapeutic levels, and the antibody was able to pass through the blood-brain barrier, which is associated with the Wnt/β- catenin pathway.

关 键 词：阿尔茨海默病 Taul95-213肽段 免疫治疗 WNT/Β-CATENIN通路 

分 类 号：R749.16[医药卫生—神经病学与精神病学]