N-乙酰神经氨酸及其复方制剂改善小鼠学习记忆功能障碍的研究

Research on the Improvement of Learning and Memory Dysfunction in Mice by N-Acetylneuraminic Acid (Neu5Ac) and Its Compound Preparation

摘要: N-乙酰神经氨酸(N-acetylneuraminic acid, NeuA5c)是一种重要的功能性单糖，作为一种内源性唾液酸，N-乙酰神经氨酸在人体内参与多种生理活动，尤其对于神经系统的发育和功能发挥着至关重要的功能。N-乙酰神经氨酸存在于多种植物、动物和微生物中。本研究旨在探讨N-乙酰神经氨酸及其复方制剂对小鼠学习记忆功能障碍的改善作用。目的：探讨N-乙酰神经氨酸及其复方制剂(含N-乙酰神经氨酸及DHA藻油和锌)在改善学习记忆功能障碍方面的功能。方法：通过东莨菪碱构建小鼠记忆障碍模型，采用Morris水迷宫、避暗实验等行为学测试，观察并记录表现，结合大脑组织的超氧化物歧化酶(SOD)、丙二醛(MDA)、乙酰胆碱(ACh)及乙酰胆碱酯酶(AChE)水平检测，评估干预效果，以探究N-乙酰神经氨酸及其复方制剂对小鼠脑内抗氧化能力和乙酰胆碱功能的影响。结果：低剂量(50 mg/kg∙bw)和高剂量(83.3 mg/kg∙bw)的N-乙酰神经氨酸及高剂量的N-乙酰神经氨酸复合制剂(Neu5Ac 26.7 mg/kg∙bw、DHA 60 mg/kg∙bw、锌1.67 mg/kg∙bw)在实验中被证实能够缓解由东莨菪碱引起的认知功能障碍，表现为显著提升小鼠在Morris水迷宫测试中的空间导航能力，路径缩短和进入次数增加。复方制剂组(Neu5Ac 26.7 mg/kg∙bw)与单方低剂量组(50 mg/kg∙bw)相比，Neu5AC含量较低，但效果更优，表明该复合制剂通过通过协同调控胆碱能系统、减轻氧化应激等机制，抑制脑内超氧化物歧化酶(SOD)活性的下降，并降低乙酰胆碱酯酶(AChE)活性，从而维持乙酰胆碱(ACh)的水平，展现出其潜在的神经保护作用。

Abstract: N-acetylneuraminic acid (NeuA5c) is an important functional monosaccharide. As an endogenous sialic acid, N-acetylneuraminic acid participates in various physiological activities within the human body, playing a crucial role in the development and function of the nervous system. N-acetylneuraminic acid is found in a variety of plants, animals, and microorganisms. This study aims to explore the improvement effects of N-acetylneuraminic acid and its compound preparations on learning and memory dysfunction in mice. Objective: To investigate the functions of N-acetylneuraminic acid and its compound preparations (containing N-acetylneuraminic acid, DHA algal oil, and zinc) in improving learning and memory dysfunction. Methods: A mouse memory impairment model was constructed using scopolamine. Behavioral tests such as the Morris water maze and the step-through test were used to observe and record performances. Combined with the detection of superoxide dismutase (SOD), malondialdehyde (MDA), acetylcholine (ACh), and acetylcholinesterase (AChE) levels in brain tissue, the intervention effects were evaluated to explore the impact of N-acetylneuraminic acid and its compound preparations on the brain’s antioxidant capacity and acetylcholine function. Results: Low-dose (50 mg/kg∙bw) and high-dose (83.3 mg/kg∙bw) N-acetylneuraminic acid and the high-dose N-acetylneuraminic acid compound preparation (Neu5Ac 26.7 mg/kg∙bw, DHA 60 mg/kg∙bw, zinc 1.67 mg/kg∙bw) were confirmed to alleviate cognitive dysfunction caused by scopolamine in the experiment. This was demonstrated by significantly improving the spatial navigation ability of mice in the Morris water maze test, with shorter paths and increased entries. Compared to the single low-dose group (50 mg/kg∙bw), the compound preparation group (Neu5Ac 26.7 mg/kg∙bw) had lower Neu5AC content but better effects. This indicates that the compound preparation, through synergistic regulation of the cholinergic system and alleviation of oxidative stress mechanisms, inhibits the decline in superoxide dismutase (SOD) activity and reduces acetylcholinesterase (AChE) activity in the brain, thereby maintaining the level of acetylcholine (ACh) and demonstrating its potential neuroprotective effects.