【目的】探讨异紫花前胡内酯对阿尔茨海默病（AD）小鼠认知障碍的改善作用及机制。【方法】将50只小鼠随机分为5组，即空白组，模型组，异紫花前胡内酯低、高剂量组及多奈哌齐（阳性药）组，每组10只。连续给药21d后，除空白组，其他各组小鼠给予腹腔注射东莨菪碱建立AD模型。采用网络药理学构建异紫花前胡内酯治疗AD共同靶点的蛋白质-蛋白质相互作用（PPI）网络，进行基因本体论（GO）及京都基因与基因组百科全书（KEGG）富集分析，提供研究方向。通过Morris水迷宫、旷场试验和新物体识别试验对AD模型小鼠认知功能进行药效评价，Nissl染色法观察海马组织神经元损伤情况，应用试剂盒检测小鼠海马乙酰胆碱（Ach）、乙酰胆碱转移酶（ChAT）、乙酰胆碱酯酶（AChE）、活性氧（ROS）、丙二醛（MDA）、过氧化氢酶（CAT）水平，采用WesternBlot法检测海马白细胞介素6（IL-6）、白细胞介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）、核因子E2相关因子2（NRF2）、沉默信息调节因子同源蛋白3（SIRT3）、Kelch样ECH关联蛋白1（KEAP1）、醌氧化还原酶1（NQO1）、血红素加氧酶1（HO-1）的蛋白表达水平。【结果】与模型组比较，异紫花前胡内酯高剂量组小鼠Morris水迷宫试验潜伏期显著缩短，旷场新物体试验进入目标区域时间、旷场中央区域运动距离延长，海马CA1和CA3区神经元数目显著增加，海马ChAT、Ach水平显著升高，AChE水平显著降低，CAT水平显著升高，ROS、MDA水平显著降低，TNF-α表达水平降低，SIRT3、HO-1表达水平升高，KEAP1蛋白表达水平降低，差异均有统计学意义（P＜0.05或P＜0.01或P＜0.001）。【结论】异紫花前胡内酯可有效改善AD小鼠认知障碍，其作用机制可能与激活NRF2/SIRT3信号通路，进而缓解氧化应激水平和神经炎症、修复胆碱能神经元功能有关。

Objective To investigate the improvement effect and mechanism of marmesin on cognitive impairment in Alzheimer’s disease（AD）mice. Methods Fifty mice were randomly divided into five groups：blank group，model group，low-and high-dose marmesin groups and donepezil（positive drug）group，with 10 mice in each group. After 21 days of continuous administration，except for the blank group，the mice in other groups were given intraperitoneal injection of scopolamine to establish the AD model. Network pharmacology was used to construct the protein-protein interaction（PPI）network of common targets of marmesin in the treatment of AD，and gene ontology（GO）and Kyoto Encyclopedia of Genes and Genomes（KEGG）enrichment analysis were performed to provide further research direction. The cognitive function of AD model mice was evaluated by Morris water maze，open field test and new object recognition test. Nissl staining was used to observe the damage of hippocampal neurons. The levels of acetylcholine（Ach），acetylcholine transferase（ChAT），acetylcholinesterase（AChE），reactive oxygen species（ROS），malondialdehyde（MDA）and catalase（CAT）in hippocampus of mice were detected by kit. The protein expression levels of interleukin 6（IL-6），interleukin 1β（IL-1β），tumor necrosis factor α（TNF-α），nuclear factor E2-related factor 2（NRF2），silent information regulator homologous protein 3（SIRT3），Kelch-like ECH-associated protein 1（KEAP1），quinone oxidoreductase 1（NQO1）and heme oxygenase 1（HO-1）in hippocampus were detected by Western Blot. Results Compared with the model group，the latency of Morris water maze test was significantly shortened in the high-dose marmesin group，the time of entering the target area in the open field new object test and the movement distance in the central area of the open field were prolonged，the number of neurons in the hippocampal CA1 and CA3 regions was significantly increased，the levels of ChAT and Ach in the hippocampus were significantly increased，AChE level was significantly decreased，CAT level was significantly increased，ROS and MDA levels were significantly decreased，TNF-α expression level was decreased SIRT3 and HO-1 expression levels were increased and KEAP1 protein expression level was decreased，the differences being statistically significant（P＜0.05 or P＜0.01 or P＜0.001）. Conclusion Marmesin can effectively improve the learning and memory impairment of AD mice，and its mechanism may be related to the activation of NRF2/SIRT3 signaling pathway，thereby alleviating oxidative stress level and neuroinflammation and repairing cholinergic neuron function.

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国家自然科学基金面上项目 （编号：82274616）；广东省科技计划国际合作项目 （编号：2020A0505100052）；广东省基础与应用基础研究基金企业联合基金 （编号：2022A1515220121）