目的 探究巴利森苷B改善慢性束缚（chronic restraint stress，CRS）所致认知功能减退的作用及潜在机制。方法 将72只ICR雄性小鼠随机分为对照组、模型组、多奈哌齐（1.6 mg/kg）组和巴利森苷B低、中、高剂量（2、4、8 mg/kg）组，每组12只。小鼠接受35 d束缚造模同时给予药物干预，第36天进行旷场实验、物体认知实验、避暗实验；采用UPLC-MS/MS方法测定海马中乙酰胆碱（acetylcholine，Ach）、谷氨酸（glutamic acid，Glu）、γ-氨基丁酸（γ-aminobutyric acid，GABA）水平；采用Western blotting检测海马脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）、磷酸化蛋白激酶B（phosphorylated protein kinase B，p-Akt）/Akt、磷酸化细胞外调节蛋白激酶（phosphorylated extracellular signal-regulated kinase，p-ERK）/ERK蛋白表达。结果 与对照组比较，模型组小鼠在新物体识别和新位置识别中的相对辨别指数显著下降（P＜0.05），入暗潜伏期显著缩短（P＜0.01），暗室时间显著增加（P＜0.001），海马中Glu水平显著升高（P＜0.01），GABA和Ach水平显著降低（P＜0.01、0.001），BDNF、p-Akt/Akt、p-ERK/ERK蛋白表达水平显著降低（P＜0.05、0.01）；与模型组比较，巴利森苷B组小鼠在新物体识别和新位置识别中的相对辨别指数显著升高（P＜0.05、0.01），入暗潜伏期显著延长（P＜0.05、0.01），暗室时间显著减少（P＜0.01、0.001），海马中Glu水平显著降低（P＜0.05），GABA和Ach水平显著升高（P＜0.01、0.001），BDNF、p-Akt/Akt、p-ERK/ERK蛋白表达水平显著升高（P＜0.05、0.01、0.001）。结论 巴利森苷B能够显著改善由CRS引起的空间、非空间认知功能障碍，其机制可能与调控神经递质、促进BDNF通路激活有关。

Objective To investigate the effect and potential mechanism of parishin B on cognitive dysfunction induced by chronic restraint stress (CRS).Methods A total of 72 male ICR male mice were randomly divided into control group, model group, donepezil (1.6 mg/kg) group and parishin B low-, medium-, high-dose (2, 4, 8 mg/kg) groups, with 12 mice in each group. Mice were subjected to 35 d of restraint modeling and drug intervention. On the 36th day, open field test, object cognition test and step-through test were conducted; Levels of acetylcholine (Ach), glutamic acid (Glu), γ-aminobutyric acid (GABA) in hippocampus were measured using UPLC-MS/MS; Protein expressions of brain-derived neurotrophic factor (BDNF), phosphorylated protein kinase B (p-Akt)/Akt and phosphorylated extracellular signal-regulated kinase (p-ERK)/ERK in hippocampus were detected by Western blotting. Results Compared with control group, the relative discrimination index in new object recognition and new position recognition of mice in model group were significantly decreased (P < 0.05), the latent period in the dark was significantly shortened (P < 0.01), the dark room time was significantly increased (P < 0.001), Glu level in hippocampus was significantly increased (P < 0.01), GABA and Ach levels were significantly decreased (P < 0.01, 0.001), and the expression levels of BDNF, p-Akt/Akt and p-ERK/ERK proteins were significantly decreased (P < 0.05, 0.01); Compared with model group, the relative discrimination index in new object recognition and new position recognition of mice in parishin B group were significantly increased (P < 0.05, 0.01), the latent period in the dark was significantly prolonged (P < 0.05, 0.01), the dark room time was significantly reduced (P < 0.01, 0.001), Glu level in hippocampus was significantly reduced (P < 0.05), GABA and Ach levels were significantly increased (P < 0.01, 0.001), and the expression levels of BDNF, p-Akt/Akt and p-ERK/ERK proteins were significantly increased (P < 0.05, 0.01, 0.001). Conclusion Parishin B could significantly improve spatial and non-spatial cognitive impairment caused by CRS, and its mechanism may be related to regulating neurotransmitters and promoting BDNF pathway activation.

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四川省科技计划项目（2021YFYZ0012）；国家自然科学基金资助项目（82274056）；中国医学科学院创新工程（2021-I2M-1-034）；新疆维吾尔自治区重大科技专项（2023A02010-3）