A number of studies have shown that early-stage Alzheimer's disease (AD) is associated with abnormal brain glucose metabolism before cognitive decline, which may be the key pathological change of asymptomatic AD. The pathogenesis of AD in traditional Chinese medicine is kidney deficiency and turbid phlegm. Based on this, GAPT (a mixture of herbal extracts) was made to invigorate kidney Yang and eliminate phlegm. Previous studies have shown that GAPT can improve and delay the memory decline, but the specific therapeutic target of AD in an early stage has not been studied. The aim of this study was to investigate the effect of GAPT on glucose metabolism in the early stage of AD. Eighty-eight 3-month-old male APP/PS1 transgenic mice were randomly divided into model group; donepezil group; and low, middle and high GAPT dosage groups. Twelve 3-month-old C57BL/6J mice were used as a control group. The Morris water maze test and the Step-Down Passive-Avoidance test were used to evaluate learning and memory ability. Cerebral extraction and the accumulation of glucose were scanned with a micro-positron-emission tomography (PET) imaging system. Immunohistochemistry, western blot analysis and polymerase chain reaction (PCR) were used to detect the expression of the PI3K/AKT-mTOR signalling pathway-related proteins and messenger RNAs (mRNAs) in hippocampus of APP/PS1 transgenic mice after 3 months of drug administration. GAPT can shorten the escape latency and error numbers compared to the model group. In micro-PET imaging analysis, GAPT can increase the glucose uptake average rate in the frontal lobe, temporal lobe, parietal lobe and hippocampus. The immunohistochemistry, western blot analysis and PCR results indicated that GAPT can increase the expression of PI3K, AKT, GLUT1 and GLUT3 in the hippocampus of APP/PS1 transgenic mice. In summary, GAPT can improve brain glucose metabolism damage in APP/PS1 transgenic mice, mainly by increasing brain glucose uptake, increasing glucose transport and improving the insulin signalling pathway.

中文翻译：

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中药复方GAPT对APP / PS1转基因小鼠早期脑葡萄糖代谢的影响。

大量研究表明，早期阿尔茨海默氏病（AD）与认知能力下降之前的脑葡萄糖代谢异常有关，这可能是无症状AD的关键病理变化。中医AD的发病机制为肾虚痰浊。在此基础上，制成GAPT（草药提取物的混合物）以增强肾阳气和消除痰液。先前的研究表明，GAPT可以改善并延缓记忆衰退，但是尚未研究早期AD的特定治疗目标。本研究的目的是研究GAPT对AD早期葡萄糖代谢的影响。将88只3个月大的雄性APP / PS1转基因小鼠随机分为模型组。多奈哌齐组 以及低，中和高GAPT剂量组。将12只3个月大的C57BL / 6J小鼠用作对照组。Morris水迷宫测试和递减被动回避测试用于评估学习和记忆能力。用微正电子发射断层扫描（PET）成像系统扫描脑提取物和葡萄糖的积累。给药3个月后，使用免疫组织化学，蛋白质印迹分析和聚合酶链反应（PCR）检测APP / PS1转基因小鼠海马中PI3K / AKT-mTOR信号通路相关蛋白和信使RNA（mRNA）的表达。 。与模型组相比，GAPT可以缩短转义潜伏期和错误数量。在微型PET成像分析中，GAPT可以提高额叶，颞叶，顶叶和海马的葡萄糖摄取平均速率。免疫组化 免疫印迹分析和PCR结果表明，GAPT可以增加APP / PS1转基因小鼠海马中PI3K，AKT，GLUT1和GLUT3的表达。总之，GAPT可以改善APP / PS1转基因小鼠的脑葡萄糖代谢损伤，主要是通过增加脑葡萄糖摄取，增加葡萄糖转运和改善胰岛素信号通路来实现的。