Graduate Institutes, Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China.
Department of Neurology, the Second Hospital Affiliated to Tianjin University of Traditional Chinese Medicine, Tianjin, 300150, China.
CNS Neurol Disord Drug Targets. 2018;17(5):389-399. doi: 10.2174/1871527317666180525113109.
Abnormal amyloid β (Aβ) accumulation and deposition in the hippocampus is an essential process in Alzheimer's disease (AD).
To investigate whether Oleanolic acid (OA) could improve memory deficit in AD model and its possible mechanism.
Forty-five SD rats were randomly divided into sham operation group, model group, and OA group. AD models by injection of Aβ25-35 were built. Morris water maze (MWM) was applied to investigate learning and memory, transmission electron microscope (TEM) to observe the ultrastructure of synapse, western blot to the proteins, electrophysiology for long-term potentiation (LTP), and Ca2+ concentration in synapse was also measured.
The latency time in model group was significantly longer than that in sham operation group (P=0.0001); while it was significantly shorter in the OA group than that in model group (P=0.0001); compared with model group, the times of cross-platform in OA group significantly increased (P=0.0001). TEM results showed OA could alleviate neuron damage and synapses changes induced by Aβ25-35. The expressions of CaMKII, PKC, NMDAR2B, BDNF, TrkB, and CREB protein were significantly improved by OA (P=0.0001, 0.036, 0.041, 0.0001, 0.0001, 0.026, respectively) compared with that in model group; the concentration of Ca2+ was significantly lower in OA group (1.11±0.42) than that in model group (1.68±0.18); and the slope rate (P=0.0001) and amplitude (P=0.0001) of f- EPSP significantly increased in OA group.
The present results support that OA could ameliorate Aβ-induced memory loss of AD rats by maintaining synaptic plasticity of the hippocampus.
海马区异常淀粉样β（Aβ）积累和沉积是阿尔茨海默病（AD）的一个重要过程。
探讨齐墩果酸（OA）是否能改善 AD 模型的记忆缺陷及其可能的机制。
将 45 只 SD 大鼠随机分为假手术组、模型组和 OA 组。通过注射 Aβ25-35 建立 AD 模型。应用 Morris 水迷宫（MWM）检测学习记忆能力，透射电镜（TEM）观察突触超微结构，Western blot 检测蛋白表达，电生理学检测长时程增强（LTP）及突触内 Ca2+浓度。
与假手术组比较，模型组潜伏期显著延长（P=0.0001）；与模型组比较，OA 组潜伏期显著缩短（P=0.0001）；OA 组穿越平台次数明显增多（P=0.0001）。TEM 结果显示 OA 可减轻 Aβ25-35 引起的神经元损伤和突触改变。OA 可显著改善 CaMKII、PKC、NMDAR2B、BDNF、TrkB、CREB 蛋白的表达（P=0.0001、0.036、0.041、0.0001、0.0001、0.026），OA 组 Ca2+浓度（1.11±0.42）明显低于模型组（1.68±0.18），f- EPSP 斜率（P=0.0001）和幅度（P=0.0001）明显增加。
本研究结果支持 OA 通过维持海马突触可塑性改善 Aβ 诱导的 AD 大鼠记忆丧失。
