外源性神经生长因子对APP/PS1转基因小鼠Wnt/β-catenin信号通路的调节  

Regulation of exogenous nerve growth factor on Wnt/β-catenin signaling pathway in the APP/PS1 transgenic mice

作　　者：杨畅[1] 张宝辉[2] 刘玉丽[3] 李宁[4] 王旭[1] 方秀斌[2] 

机构地区：[1]辽宁中医药大学解剖学组织学胚胎学教研室,沈阳110847 [2]中国医科大学神经生物学教研室,沈阳110001 [3]辽宁中医药大学针灸推拿学院,沈阳110847 [4]辽宁中医药大学重大科研平台,沈阳110847

出　　处：《解剖学杂志》2015年第2期129-132,152,共5页Chinese Journal of Anatomy

基　　金：国家自然科学基金(81100810)

摘　　要：目的：探讨外源性神经生长因子（NGF）对APP/PS1转基因小鼠Wnt/β-catenin信号通路的调节.方法：鼻腔给予小鼠NGF治疗14周,应用免疫组织化学检测小鼠脑内β淀粉样蛋白（Aβ）老年斑的分布,应用免疫印迹检测小鼠脑内糖原合酶激酶3β（GSK3β）、p-GSK3β、β-连环蛋白（β-catenin）和p-β-catenin的表达.结果：Aβ免疫组织化学显色结果显示,与对照组小鼠大脑内的Aβ老年斑相比较,NGF治疗组转基因小鼠大脑内的Aβ老年斑数量减少了30.22％,沉积减少了35.85％,差异有统计学意义.免疫印迹结果显示,外源性NGF减少APP/PS1转基因小鼠脑内GSK3β的表达,增加β-catenin的表达.结论：外源性NGF可能通过抑制GSK3β的活性和增加β-catenin的活性,激活Wnt/β-catenin信号通路,对神经元起保护作用.Objective： To study the regulation of exogenous nerve growth factor （NGF） on Wnt/β-catenin signaling pathway in the APP/PS1 transgenic mice. Methods： The mice were treated with NGF via the nasal cavity for 14 weeks. Immunohistochemistry was applied to examine the distribution of Aβ plaques in the APP/PS1 mice brains. Western blotting was used to test the expressions of GSK313, p-GSK3β, β-catenin and p-β-catenin in the mice brains. Results： Immunohistochemical staining showed that compared with the control group, the number of Aβ senile plaques in the NGF treatment mice brains was reduced by 30.22% and the deposition of senile plaques was decreased by 35.85%. Western blotting showed that exogenous NGF reduced the expressions of GSK313 and increased the expressions of β-catenin in the APP/ PS1 transgenic mice brains. Conclusion： Exogenous NGF has a neuroprotective effect on the APP/PS1 transgenic mice by activating the Wnt/β-catenin signaling pathway.

关 键 词：APP/PS1转基因小鼠 神经生长因子 糖原合酶激酶3Β Β-连环蛋白 WNT/Β-CATENIN信号通路 

分 类 号：R749.16[医药卫生—神经病学与精神病学]