摘要： 目的 探讨烟酰胺单核苷酸(NMN)对阿尔茨海默病(AD)模型大鼠认知功能的影响及其神经保护机制。方法 选择清洁级雄性Wistar大鼠36只,随机分为假手术组、AD组和AD+NMN组,每组l2只。药物处理6周后,采用Morris水迷宫实验检测各组大鼠的认知功能,苏木精-伊红(HE)染色检测海马神经细胞死亡,利用免疫荧光法检测海马CA1区烟酰胺腺嘌呤二核苷酸(NAD⁺)水平。结果 与假手术组比较,AD组逃避潜伏期明显延长,象限活动时间和穿越次数明显减少,海马CA1区神经细胞内NAD⁺水平显著降低,海马CA1区神经细胞死亡增加,差异有统计学意义(P<0.05)。与AD组比较,AD+NMN组逃避潜伏期均明显缩短,象限活动时间和穿越次数明显增加,海马CA1区神经细胞死亡显著减少,神经细胞内NAD⁺水平显著增加,差异均有统计学意义(均P<0.05)。结论 NMN可明显提高AD模型大鼠学习记忆能力水平,改善认知功能障碍,显著减少海马神经细胞死亡;NMN可能通过增加海马组织内NAD⁺的水平发挥其神经保护作用。

烟酰胺单核苷酸对阿尔茨海默病模型大鼠认知功能的影响

王晓楠, 张励, 徐茜, 杨旸, 胡雪君

中国医科大学附属第一医院老年医学科, 沈阳 110001

收稿日期:2019-11-19出版日期:2020-06-30发布日期:2020-06-15
通讯作者:王晓楠E-mail:xiao_nan99@hotmail.com
作者简介:王晓楠(1981-),女,副主任医师,博士.
基金资助:国家自然科学基金（81200246）


关键词: 烟酰胺单核苷酸, 阿尔茨海默病, 认知功能, 神经细胞死亡
Abstract: Objective To explore the effects of nicotinamide mononucleotide (NMN) on the cognitive function of rats with Alzheimer disease (AD) and the mechanism of neuroprotection. Methods A total of 36 rats were randomly divided into the control group,AD model group,and AD+NMN group (n=12 each group). The rat's learning and memory abilities were tested using a Morris water maze.Hematoxylin and eosin (HE) staining was used to quantify neuronal death of the hippocampus. The NAD⁺ was measured after its enzymatic conversion to NADH using alcohol dehydrogenase. Results Compared to the control group,the AD model group displayed significantly prolonged escaping delitescence,significantly reduced activity time on the former platform quadrant,significantly reduced crossings of the former platform,decreased NAD⁺ levels in the hippocampal slices and significantly increased neuronal cell death in the CA1 of the hippocampus (respectively,P<0.05). Compared to the AD model group,the AD+NMN group displayed a significantly improved general condition,significantly shortened escape latency (P<0.05),significantly increased activity time on the former platform quadrant (P<0.05),significantly increased crossings of the former platform (P<0.05),significantly decreased neuronal cell death in the CA1 of the hippocampus (P<0.05) and restored NAD⁺ levels (P<0.05). Conclusion NMN could ameliorate cognitive impairment and decrease the neuronal cell death of rats with AD. NMN could restore the NAD⁺ levels,providing neuronal protection.
Key words: nicotinamide mononucleotide, Alzheimer disease, cognitive function, neuronal cell death
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