EGCG通过NGF/TrkA通路影响APP/PS1小鼠脑内Aβ沉积的研究  

Effects on Aβdepositionin in brains of APP/PS1 transgenic mice by EGCG through NGF/Trk Asignaling pathway

作　　者：钟欣[1] 刘明妍[1] 姚维凡[1] 杜可[1] 杨时伦 赵海山[1] 魏敏杰[1] 

机构地区：[1]中国医科大学药理教研室

出　　处：《中国神经免疫学和神经病学杂志》2016年第2期104-108,共5页Chinese Journal of Neuroimmunology and Neurology

基　　金：国家科技部"重大新药创制"科技重大专项子课题(2013ZX09103001-003);辽宁省教育厅科学研究一般项目(L2012279);辽宁省科学技术计划项目(2013225079)

摘　　要：目的探讨绿茶的有效多酚成分表没食子儿茶素没食子酸酯(EGCG)对淀粉样前体蛋白/早老素基因(APP/PS1)转基因小鼠脑内β-淀粉样蛋白(Aβ)沉积及其对海马内神经生长因子(NGF)相关神经生长因子受体(TrkA)信号通路的影响。方法采用免疫组化及Western blot法分别检测小鼠海马Aβ1-40、淀粉样前体蛋白(APP)的蛋白表达水平,Western blot检测小鼠海马NGF及神经生长因子前体(proNGF)的表达水平及其共同受体TrkA下游细胞外信号调节激酶(ERK)通路相关蛋白的表达水平。结果免疫组化结果显示,模型组小鼠海马内Aβ1-40和APP表达(42.35±8.25、143.63±24.30)较对照组(13.04±4.36、19.89±4.93)均显著增加(均P<0.05),治疗组(19.72±6.55、38.07±18.19)较模型组明显降低(均P<0.05)。Western blot结果显示,与对照组(均为100)比较,模型组小鼠海马内Aβ1-40、APP的相对表达量增加(分别为363.39±45.77、499.51±65.75,均P<0.01),与模型组比较,治疗组Aβ1-40、APP相对表达量显著降低(分别为179.77±18.17、160.42±44.55,均P<0.01)。与对照组(均为100)比较,模型组NGF(16.39±4.03)、pro-NGF(25.92±5.37)、NGF/pro-NGF(63.64±10.68)、p-TrkA(7.92±2.13)、p-c-raf(7.37±2.66)、p-ERK1/2(13.53±4.44)及pCREB(3.95±1.56)的相对表达量降低(均P<0.05);与模型组比较,治疗组NGF(80.78±12.18)、pro-NGF(48.63±3.83)、NGF/pro-NGF(165.84±19.02)、p-TrkA(72.33±6.21)、p-c-raf(88.12±5.33)、p-ERK1/2(60.21±10.34)及p-CREB(25.31±8.48)的相对表达量明显增加(均P<0.05)。治疗组与对照组上述指标比较差异均无统计学意义(均P>0.05)。结论 EGCG主要通过上调NGF/proNGF比例,增加NGF的相对表达,继而激活其下游特异性TrkA通路,显著增加TrkA、c-raf、ERK1/2及其下游效应蛋白CREB的磷酸化水平,从而抑制Aβ1-40和APP的表达,改善学习记忆障碍,发挥神经保护作用。Objective To discuss the effects of（-）-epigallocatechin-3-gallate（EGCG）in green tea on Aβdeposition in brains of Amyloid precursor protein/presenilin-1gene（APP/PS1）transgenic mice and the related nerve growth factor（NGF）/tyrosine kinase A（TrkA）signaling pathway in the hippocampus.Methods Immunohistochemistry and Western blot methods were used to detect the levels of Aβ1-40 and APP in the hippocampus of APP/PS1 transgenic mice.The expressions of NGF and pro-NGF in the hippocampus were detected by Western blot,as well as the expression levels of its receptor TrkA and the downstream of the extracellular signal-regulated kinase（ERK）pathway.Results Immunohistochemical detection showed that the expressions of Aβ1-40 and APP of the model group（42.35±8.25,143.63±24.30）increased compared with the control group（13.04±4.36,19.89±4.93,P〈0.05,respectively）,while the expression levels of the treatment group（19.72±6.55,38.07±18.19）were far lower than the model group（P〈0.05,respectively）.Western blot results showed that compared with the control group（100,respectively）,the relative expressions of Aβ1-40 and APP of the model group increased（363.39±45.77,499.51±65.75,P〈0.01,respectively）and NGF（16.39±4.03）,pro-NGF（25.92±5.37）,NGF/pro-NGF（63.64±10.68）,p-TrkA（7.92±2.13）,pc-raf（7.37 ± 2.66）,p-ERK1/2（13.53 ± 4.44）and p-CREB（3.95 ± 1.56）decreased（P 0.05,respectively）.The relative expression levels of Aβ1-40 and APP of the treatment group179.77±18.17,160.42±44.55,P〈0.01,respectively）were much lower than the model group,while the relative expression levels of NGF（80.78±12.18）,pro-NGF（48.63±3.83）,NGF/pro-NGF（165.84±19.02）,p-TrkA（72.33±6.21）,p-c-raf（88.12±5.33）,p-ERK1/2（60.21±10.34）and p-CREB（25.31±8.48）of the treatment group were significantly higher than the model group（P 0.05,respectively）.There were no significant differences between the treatment group and the control group（P〉0.05,r

关 键 词：表没食子儿茶素没食子酸酯 神经生长因子 TRKA APP/PS1转基因小鼠 Β-淀粉样蛋白 

分 类 号：R741.02[医药卫生—神经病学与精神病学]