快速老化小鼠P10海马PI3K信号转导通路的变化及APP17肽的影响

目的探讨APP17肽对快速老化小鼠P10（SAMP10）学习记忆、海马组织抗氧化酶活性和PI3K信号转导通路蛋白质变化的影响。方法采用通道式水迷宫实验观察SAMP10行为学改变，采用羟胺法和硫代巴比妥酸（TBA）比色法、黄嘌呤氧化酶法及免疫组织化学染色技术，测定过氧化脂质降解产物中丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性、PI3K信号转导通路蛋白质的变化。结果①模型组小鼠存在明显的学习记忆功能障碍，APP17肽治疗组小鼠的行为学障碍明显轻于模型组与正常对照组无明显差异；②模型组海马神经细胞线粒体SOD活性明显降低（P<0.01），MDA含量显著升高（P<0.01）；APP17肽组SOD活性高于模型组（P<0.05），而MDA含量低于模型组（P<0.01）；③模型组PI3K信号转导通路相关蛋白TrkA、Akt/PKB、bcl 2阳性染色细胞数较对照组分别减少63%、50%和45%(P<0.01)，经APP17肽治疗后，各种蛋白的表达明显上调(P<0.05)；而神经生长因子（NGF）和结合元件蛋白（CREB）的表达无明显差异（P>0.05）。结论SAMP10存在学习记忆障碍，海马组织抗氧化酶活性降低、自由基代谢产物含量增加、PI3K信号转导通路蛋白表达异常，APP17肽能部分纠正这些异常变化。

Variation of PI3K signal transduction pathway relative protein in SAMP10(senescence accelerated mice/prone 10) and effect of APP17 peptide

To investigate effects of APP17 peptides (β Amyloid precursor protein, APP, 319 335 peptide fragment) on SAMP10(senescence accelerated mice/prone 10) learning memorizing, hippocampus tissue antioxidase activity, and the PI3K signal transduction pathway proteins in mice.  MethodLearning and memorizing variations were observed by a water maze test, malonaldehyde(MDA) contents in oxidized lipid degradation products were determined using the hydroxylamine and barbituric acid(TBA) method, erythrocuperin(SOD) activity using an xanthine oxidase method， and the PI3K signal transduction pathway proteins using immunohistochemical staining.  Results(1)Water maze results showed that evident learning and memorizing dysfunction existed in the model group. Ethological dysfunction in the APP17 peptide treatment group， which had no apparent differences compared with the normal controls， was evidently slighter than that in the model group. (2) SOD activity of mice hippocampus neurocyte mitochondria in the model group was manifestly degraded (P<0.01)，and MDA contents were markedly elevated compared with the normal controls (P<0.01). SOD activity was higher in the APP17 peptide treatment group than in the model group (P<0.05)，whereas MDA contents were lower in the APP17 peptide treatment group than in the model group(P<0.01). (3)Immunohistochemistry results showed that positive staining cell population of the relative protein TrkA, Akt/PKB, and bcl 2 in mice hippocampus neurocyte PI3K signal transduction pathway was respectively reduced by 63%, 50% and 45% compared with the control group (P<0.01). After APP17 peptide therapy, expression of the above mentioned proteins was evidently up regulated (P<0.05)；expressions of NGF and CREB had no apparent differences(P>0.05). ConclusionLearning dysmnesia, reduced hippocampus tissue antioxidase activity, increased free radical metabolic product contents and abnormalexpression of PI3K signal transduction pathway protein existed in SAMP10(senescence accelerated mice/prone 10), which can be partially rectified by APP17.