Fu Ying, Wei Jiangping, Li Bin, Gao Lijuan, Xia Peng, Wen Yueqiang, Xu Shijun
School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China.
Institute of Meterial Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China.
Exp Ther Med. 2020 Nov;20(5):70. doi: 10.3892/etm.2020.9198. Epub 2020 Sep 9.
Multi infarct dementia (MID) is a form of dementia that is preventable and treatable. However, at present, the drugs used in MID treatment were developed for Alzheimer's disease. While only a limited range of drugs is available, the incidence of MID is increasing year on year. The present study aimed to investigate the effect and underlying mechanisms of a combination of ginsenosides and astragalosides (CGA) on cognitive decline in rats with MID. A rat model of MID was established using micro-thromboembolism, and the behavioral changes in the rats were evaluated using the Morris water maze and open field tests at 60 days post-CGA intervention. The pathological morphology of the hippocampal CA1 area was observed using hematoxylin and eosin staining. The contents of ATP, ADP and AMP were determined using high-performance liquid chromatography. Mitochondrial swelling and changes in the membrane potential in the hippocampus were detected using flow cytometry, and the changes in insulin, glutamate and γ-aminobutyric acid (GABA) content were detected using ELISA. Additionally, the expression of PI3K and AKT proteins was detected using western blot analysis. In a rat model of MID, CGA shortened the escape latency, increased the frequency of platform crossing, improved the disordered vertebral cell arrangement and reduced the cell number in the hippocampal CA1 area. CGA also reduced the degree of mitochondrial swelling, increased the mitochondrial membrane potential, and elevated the energy load and ATP content in the brain of rats with MID. Furthermore, CGA increased the insulin content and upregulated the expression of PI3K and AKT in the brain of rats with MID. In addition, in the rat model of MID, CGA also enhanced the movement time and the frequency of standing, and decreased the concentration of glutamate and GABA in the brain tissue. Amelioration of the cognitive decline in rats with MID by CGA was associated with its regulatory effect on the PI3K/AKT signaling pathway and neurotransmitter systems.
多发性梗死性痴呆（MID）是一种可预防和治疗的痴呆形式。然而，目前用于MID治疗的药物是针对阿尔茨海默病开发的。虽然可用药物种类有限，但MID的发病率却逐年上升。本研究旨在探讨人参皂苷和黄芪皂苷组合（CGA）对MID大鼠认知功能衰退的影响及其潜在机制。采用微血栓栓塞法建立MID大鼠模型，并在CGA干预60天后，通过莫里斯水迷宫和旷场试验评估大鼠的行为变化。采用苏木精-伊红染色观察海马CA1区的病理形态。采用高效液相色谱法测定ATP、ADP和AMP的含量。采用流式细胞术检测海马线粒体肿胀及膜电位变化，采用酶联免疫吸附测定法检测胰岛素、谷氨酸和γ-氨基丁酸（GABA）含量变化。此外采用蛋白质免疫印迹分析检测PI3K和AKT蛋白的表达。在MID大鼠模型中，CGA缩短了逃避潜伏期，增加了穿越平台的次数，改善了椎体细胞排列紊乱，并减少了海马CA1区的细胞数量。CGA还减轻了线粒体肿胀程度，增加了线粒体膜电位，并提高了MID大鼠脑内的能量负荷及ATP含量。此外，CGA增加了MID大鼠脑内胰岛素含量，并上调了PI3K和AKT的表达。另外，在MID大鼠模型中，CGA还延长了运动时间和站立频率，并降低了脑组织中谷氨酸和GABA的浓度。CGA改善MID大鼠的认知功能衰退与其对PI3K/AKT信号通路和神经递质系统的调节作用有关。
