Ni Jing-Nian, Shi Jing, Zhang Xue-Kai, Yang Yi-Chang, Liu Xiao-Meng, Wei Ming-Qing, Li Ting, Wang Peng-Wen, Tian Jin-Zhou, Wang Yong-Yan
Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
Key Laboratory of Chinese Internal Medicine, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.
Chin J Integr Med. 2017 Aug;23(8):605-610. doi: 10.1007/s11655-017-2545-7. Epub 2017 Jun 20.
To investigate the effect of GAPT, an extract mixture from Radix Ginseng, Rhizoma Acor tatarinowii, Radix Polygalae and Radix Curcuma (containing ingredient of turmeric), etc. on expression of tau protein and its phosphorylation related enzyme in hippocampal neurons of APPV717I transgenic mice.
Sixty three-month-old APPV717I transgenic mice were randomly divided into model group, donepezil group [0.92 mg/(kg•d)], the low, medium and high dosage of GAPT groups [0.075, 0.15, 0.30 g/(kg•d), 12 in each group], and 12 three-month-old C57BL/6J mice were set as a normal control group, treatments were administered orally once a day respectively, and both the normal group and model group were given 0.5% sodium carboxymethyl cellulose solution. Immunohistochemistry (IHC) and Western blot analysis were used to detect the expression of total tau protein (Tau-5), cyclin-dependent kinase 5 (CDK5) and protein phosphatase 2A (PP2A) in hippocampal neurons of experimental mice after 8-month drug administration (11 months old).
In the model group, the expression of Tau-5 and CDK5 were increased, whereas the expression of PP2A was decreased in hippocampal neurons, which were signifificantly different compared with that in the normal group (all P<0.01). IHC test indicated the number and area of either Tau-5 or CDK5 positive cells were decreased with a dose-depended way in GAPT groups, and an increase of PP2A. Compared with the model group, the changes were signifificant in GAPT groups (P<0.05 or P<0.01). Similar results were shown by Western blot.
GAPT could attenuate abnormal hyperphosphorylation of tau protein in hippocampal neurons of APPV717I transgenic mice via inhibiting the expression of CDK5 and activating the expression of PP2A.
研究人参、石菖蒲、远志及莪术提取物混合物（含姜黄成分，简称GAPT）对APPV717I转基因小鼠海马神经元tau蛋白及其磷酸化相关酶表达的影响。
将60只3月龄APPV717I转基因小鼠随机分为模型组、多奈哌齐组[0.92毫克/（千克·天）]、GAPT低、中、高剂量组[0.075、0.15、0.30克/（千克·天），每组12只]，另设12只3月龄C57BL/6J小鼠作为正常对照组，各组分别每日灌胃给药1次，正常组和模型组给予0.5%羧甲基纤维素钠溶液。给药8个月（11月龄）后，采用免疫组织化学（IHC）和蛋白质印迹法检测实验小鼠海马神经元中总tau蛋白（Tau-5）、细胞周期蛋白依赖性激酶5（CDK5）和蛋白磷酸酶2A（PP2A）的表达情况。
模型组海马神经元中Tau-5和CDK5表达增加，而PP2A表达降低，与正常组相比差异有统计学意义（均P<0.01）。IHC检测显示，GAPT各剂量组Tau-5或CDK5阳性细胞数量及面积均呈剂量依赖性减少，PP2A增加。与模型组比较，GAPT各剂量组差异有统计学意义（P<0.05或P<0.01）。蛋白质印迹法结果与之相似。
GAPT可能通过抑制CDK5表达、激活PP2A表达减轻APPV717I转基因小鼠海马神经元tau蛋白异常过度磷酸化。
