油酰乙醇胺对东莨菪碱诱导小鼠认知功能损伤的保护作用

目的 探讨油酰乙醇胺对东莨菪碱诱导小鼠认知功能损伤的保护作用。方法 将小鼠随机分为6组：对照组、模型组、多奈哌奇组（阳性药，3 mg·kg^-1）和油酰乙醇胺低、中、高剂量（50、100、200 mg·kg^-1）组，每组6只。在ig给药4周后，除对照组外，各组ip 3 mg·kg^-1的东莨菪碱建立阿尔茨海默病（AD）模型。避暗、跳台行为学实验检测小鼠记忆功能； ELISA法检测小鼠海马和大脑皮层中乙酰胆碱（Ach）和乙酰胆碱酯酶（AChE）水平；HE染色观察小鼠大脑皮层及海马损伤。结果 与对照组比较，模型组的避暗潜伏期显著缩短、避暗错误次数显著增加（P<0.001）；大脑皮层、海马的Ach水平显著减少（P<0.01、0.001），AChE活性显著升高（P<0.001）；模型组的小鼠脑组织形态结构不均匀，组织细胞呈弥散状，提示组织存在病变。与模型组比较，各给药组的避暗潜伏期显著升高、避暗错误次数显著减少（P<0.01）；油酰乙醇胺给药组的小鼠大脑皮层、海马组织Ach水平显著升高（P<0.05、0.01），AChE活性显著降低（P<0.01、0.001）；小鼠脑组织形态结构病理改变减轻。结论 油酰乙醇胺对东莨菪碱诱导学习记忆障碍模型小鼠的认知功能具有改善作用，其作用机制可能与调节胆碱能系统功能、促进神经细胞存活有关。

Protective effect of N-oleoylethanolamine on scopolamine-induced cognitive impairment in mice

Objectives To explore the protective effect of N-oleoylethanolamine alleviates scopolamine-induced spatial learning and memory deficits in mice. Methods The mice were randomly divided into six groups:control group, model group, donepezil group (positive drug, 3 mg·kg^-1) and N-oleoylethanolamine low, medium and high dose (50, 100, 200 mg·kg^-1) groups, with six mice in each group. Four weeks after ig administration, except for the control group, dementia models were established by ip 3 mg·kg^-1 of scopolamine in each group. Test the memory function of mice through behavioral experiments of avoiding darkness and jumping platforms. The levels of acetylcholine (Ach) and acetylcholinesterase (AChE) in hippocampus and cerebral cortex of mice were detected by ELISA. HE staining was used to observe the damage to the cerebral cortex and hippocampus of mice. Results Compared with the control group, the model group had a significantly shorter latency and an increased number of avoidance errors (P < 0.001), the levels of Ach in the cerebral cortex and hippocampus were significantly reduced (P < 0.01, 0.001), while the activity of AChE was significantly increased (P < 0.001), the brain tissue morphology and structure of the model group mice were uneven, with diffuse tissue cells, indicating the presence of pathological changes in the tissue. Compared with model group, the latency of dark avoidance significantly increased and the number of dark avoidance errors significantly decreased in each medication group (P < 0.01), Ach level in cerebral cortex and hippocampus of mice in N-oleoylethanolamine administration group was significantly increased (P < 0.05, 0.01), and AChE activity was significantly reduced (P < 0.01, 0.001), and the pathological changes in the morphology and structure of mouse brain tissue were alleviated. Conclusion N-oleoylethanolamine can improve the cognitive function of scopolamine-induced learning and memory impairment model mice. The effect of N-oleoylethanolamine may be related to regulating the function of the cholinergic system and promoting the survival of nerve cells.