1 Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine (BUCM), Beijing, China.
2 Key Laboratory of Pharmacology, State Administration of Traditional Chinese Medicine, Dongzhimen Hospital, Beijing University of Chinese Medicine (BUCM), Beijing, China.
Int J Immunopathol Pharmacol. 2018 Jan-Dec;32:2058738418780066. doi: 10.1177/2058738418780066.
Reduced glucose utilization and deficient energy metabolism that occur in the early stages of Alzheimer's disease correlate with impaired cognition, and this information is evidence that Alzheimer's disease is a metabolic disease that is associated with brain insulin/insulin-like growth factor resistance. This research aimed to investigate the effects of Banxia Xiexin decoction (BXD) on cognitive deficits in APPswe/PS1dE9 double transgenic mice and verify the hypothesis that BXD treatment improves cognitive function via improving insulin signalling, glucose metabolism and synaptic plasticity in the hippocampus of APPswe/PS1dE9 double transgenic mice. We used 3-month-old APPswe/PS1dE9 double transgenic mice as the case groups and wild-type littermates of the double transgenic mice from the same colony as the control group. Forty-five APPswe/PS1dE9 double transgenic mice were randomly divided into the model group, donepezil group and BXD group. The mice in the control and model groups were administered 0.5% carboxymethyl cellulose orally. The Morris water maze and step-down test were conducted to evaluate the cognitive performance of APPswe/PS1dE9 double transgenic mice after BXD treatment. Ultrastructure of synapses was observed in the hippocampal CA1 area. Proteins involved in insulin signalling pathways and glucose transports in the hippocampus were assessed through immunohistochemical staining and western blot. After 3 months intervention, we found that BXD treatment improved cognitive performance and the synaptic quantity and ultrastructure, restored insulin signalling and increased the expression of glucose transporter 1 (GLUT1) and GLUT3 levels. These findings suggest that the beneficial effect of BXD on cognition may be due to the improvement of insulin signalling, glucose metabolism and synaptic plasticity.
阿尔茨海默病早期出现的葡萄糖利用率降低和能量代谢不足与认知障碍相关，这一信息表明阿尔茨海默病是一种与大脑胰岛素/胰岛素样生长因子抵抗相关的代谢疾病。本研究旨在探讨半夏泻心汤（BXD）对 APPswe/PS1dE9 双转基因小鼠认知缺陷的影响，并验证 BXD 治疗通过改善 APPswe/PS1dE9 双转基因小鼠海马胰岛素信号、葡萄糖代谢和突触可塑性来改善认知功能的假说。我们使用 3 月龄 APPswe/PS1dE9 双转基因小鼠作为病例组，同窝野生型双转基因小鼠作为对照组。将 45 只 APPswe/PS1dE9 双转基因小鼠随机分为模型组、多奈哌齐组和 BXD 组。对照组和模型组小鼠给予 0.5%羧甲基纤维素口服。Morris 水迷宫和跳台实验用于评估 BXD 治疗后 APPswe/PS1dE9 双转基因小鼠的认知表现。观察海马 CA1 区突触的超微结构。通过免疫组化染色和 Western blot 评估海马胰岛素信号通路和葡萄糖转运蛋白相关蛋白。经过 3 个月的干预，我们发现 BXD 治疗改善了认知表现和突触数量及超微结构，恢复了胰岛素信号，增加了葡萄糖转运蛋白 1（GLUT1）和 GLUT3 的表达。这些发现表明，BXD 对认知的有益作用可能是由于改善了胰岛素信号、葡萄糖代谢和突触可塑性。
