目的 观察五味子醇甲对记忆障碍模型小鼠学习记忆的改善作用并探讨其机制。方法 在整体水平，五味子醇甲（0.5、1.0、2.0 g·kg-1·d-1）连续灌胃14 d后，以戊巴比妥钠（20 mg·kg-1）建立小鼠记忆障碍模型，采用Morris水迷宫法检测小鼠学习记忆能力；测定脑组织超氧化物歧化酶（superoxide dismutase，SOD）、一氧化氮（nitric oxide，NO）、过氧化氢酶（catalase， CAT）的活性；免疫组化分析核转录因子-κB（NF-κB）、乙酰胆碱转移酶（choline acetyltransferase， ChAT）、脑源性神经营养因子（brain-derived neurotrophic factor ，BDNF）的表达。在细胞水平，以PC12为靶细胞，以过氧化氢（H₂O₂）诱导细胞凋亡，以五味子醇甲（0.3，0.6，1.2 μmol·L-1）进行预保护24 h，检测PC12细胞活性及细胞上清液中NO的变化；细胞免疫化学染色检测PC12细胞中bcl-2的表达；Western blot方法检测bax的表达。结果 与模型组比较，五味子醇甲可延长小鼠有效区停留时间、增加小鼠穿越平台的次数；提高小鼠脑内CAT的活性、SOD活性并降低NO含量（P＜0.05，P＜0.01）。免疫组化结果显示，五味子醇甲可增加海马区ChAT蛋白表达、BDNF的蛋白表达、抑制NF-kB蛋白的核表达，与模型组比较有统计学差异（P＜0.05，P＜0.01）。五味子醇甲可提高PC12细胞的存活率并降低其细胞上清液中NO的浓度，与H₂O₂模型组比较有差异（P＜0.05，P＜0.01）；细胞免疫化学染色提示五味子醇甲可增加bcl-2的表达量，Western blot 结果表明，高剂量组五味子醇甲可降低bax蛋白表达量。结论 五味子醇甲具有改善记忆障碍模型小鼠学习记忆的作用，其机制可能与抑制NF-κB的核转录、增加BDNF的表达而有效降低脂质过氧化产物水平有关；亦可通过增强海马区ChAT的表达，增加ACh递质的合成；或是在细胞水平调节Bcl-2家族蛋白的表达等多种途径有关。

OBJECTIVE To observe the effects of schizandrol A on the learning and memory disorder in mice， and to explore its mechanism. METHODS The memory impairment model was established by using pentobarbital sodium（20 mg·kg-1）intraperitoneally injected in mice. Schizandrol A （0.5，1.0，2.0 g·kg-1·d-1） was administered through gavage for consecutive 14 d. Morris Water Maze test was used to evaluate the impairment of learning and memory. The activity of superoxide dismutase （SOD）， nitric oxide （NO） and catalase （CAT） of brain tissue were measured. The positive expression of nuclear transcription factor-κB （NF-κB）， choline acetyltransferase （ChAT）， brain-derived neurotrophic factor （BDNF） in the hippocampus CA1 region were determined by immunohistochemical analysis. At the cellular level， with schizandrol A （0.3，0.6，1.2 μmol·L-1） pre-administered 24 h， the PC12 cell apoptosis model was induced by H₂O₂. And PC12 cell activity was detected by thiazole blue （MTT） colorimetric assay， the activity of NO in cell serum were measured. The expression of bax was determined by combination of western blotting and image analysis software. The bcl-2 expression was detected by immunocytochemical staining. RESULTS Morris Water Maze test showed that， during the spatial probe trial on the fifth day， the mice in the model group had shorter residence time and less crossing times on the previous flat area than those in the control group （P <0.05）， which could be prolonged after schisandrin treatment （P＜0.05，P＜0.01）. Analysis of brain tissues showed that， compared with the control group， NO level increased and SOD， CAT activity decreased in the model group （P <0.01）. After being treated with schizandrol A， the NO level significantly decreased （P <0.01）， while SOD and CAT activity increased （P<0.01）.Immunohistochemistry analysis showed that the protein expression of ChAT and BDNF in the hippocampal CA1 region decreased in the model group， the protein expression of NF-κB significantly increased after modeling， while schizandrol A（1.0 g·kg-1） significantly increased the protein expression of ChAT and BDNF， and inhibited the protein expression of NF-κB（P＜0.05，P＜0.01）. At the cellular level， compared with the H₂O₂ model group， schizandrol A（0.6，1.2 μmol·L-1） significantly increased PC12 cell viability and decreased the NO level（P＜0.05，P＜0.01). Compared with the H₂O₂ model group， the expression of Bcl-2 in the schizandrol A group（1.2 μmol·L-1） was up-regulated and the expression of bax was down-regulated. CONCLUSION Schizandrol A could improve the learning-memory dysfunction in mice induced by sodium pentobarbital intraperitoneally injected， and its protective mechanism is related to the effect of lowering oxidative damage and inhibiting the cell apoptosis through up-regulating the expression of Bcl-2 and down-regulating the expression of bax and improving the synthesis of neurotransmitters through increasing the expression of ChAT in the hippocampal CA1 region.