摘要： 目的 观察远志总皂苷对阿尔茨海默病模型大鼠海马CA1 区脑源性神经营养因子（BDNF）及其特异性受体酪氨酸蛋白激酶B（TrkB）表达的影响，探讨远志总皂苷对阿尔茨海默病的干预作用机制。方法 雄性Wistar 大鼠被随机分为生理盐水组（正常对照组）、阿尔茨海默病模型组（模型组），以及远志总皂苷低剂量（12.50 mg/ml）和高剂量（37.50 mg/ml）组；采用D-半乳糖致衰老联合鹅膏覃氨酸损毁基底前脑Meynert 核法建立阿尔茨海默病大鼠模型，免疫组织化学染色检测大鼠海马CA1 区BDNF 及其受体TrkB 表达水平。结果 BDNF 和TrkB 阳性物质呈棕黄色，主要表达于海马CA1 区神经元胞膜。模型组大鼠海马CA1 区BDNF 及其受体TrkB 表达水平为0.30 ± 0.02 和0.21 ± 0.07，低于正常对照组的0.47 ± 0.02 和0.46 ± 0.05（均P = 0.000）；与模型组相比，远志总皂苷低剂量组（0.35 ± 0.05，0.32 ± 0.07）和高剂量组（0.43 ± 0.05，0.37 ± 0.03）大鼠海马CA1区BDNF 及其受体TrkB 表达水平均显著升高（均P = 0.000），但以高剂量组升高更为显著（均P = 0.000）。结论 远志总皂苷可以显著升高阿尔茨海默病模型大鼠海马CA1 区BDNF 及其受体TrkB 表达水平，且具有剂量依赖性，这可能是其改善认知功能的机制之一。

关键词: 远志, 皂苷类, 阿尔茨海默病, 海马, 脑源性神经营养因子, 受体蛋白质酪氨酸激酶类, 疾病模型, 动物

Abstract: Objective To investigate the effects of tenuigenin (TEN) on expression of brain-derived neurotrophic factor (BDNF), and its receptor tyrosine protein kinase B (TrkB) in the hippocampal CA1 region of Alzheimer's disease (AD) model rats.  Methods  Sixty male Wistar rats were divided randomly into 4 groups: the control group, the model group, 12.50 mg/ml TEN group and 37.50 mg/ml TEN group. AD model rats were made by injecting ibotenic acid into Meynert basal nuclei of aging rats induced by D-galactose. The expressions of BDNF and its receptor TrkB in the hippocampal CA1 region were measured by immunohistochemistry method.  Results  The positive expressions of BDNF and TrkB were pale brown and mainly in neuronal cell membrane of the hippocampal CA1 region measured by immunohistochemistry method. The average absorbance values of BDNF and its receptor TrkB in the control group were 0.47 ± 0.02 and 0.46 ± 0.05, while in the model group were 0.30 ± 0.02 and 0.21 ± 0.07 which were significantly lower than that of the control group (P = 0.000, for all). The average absorbance values of BDNF and its receptor TrkB in 12.50 mg/ml TEN group were 0.35 ± 0.05 and 0.32 ± 0.07, which were significantly higher than that of the model group (P = 0.000, for all) and 37.50 mg/ml TEN group were 0.43 ± 0.05 and 0.37 ± 0.03, which were significantly higher than that of the model group (P = 0.000, for all). The average absorbance values of BDNF and its receptor TrkB in 37.50 mg/ml TEN group increased significantly than that in 12.50 mg/ml TEN group (P = 0.000).  Conclusions  TEN can dose-dependently increase BDNF and its receptor TrkB expression in the hippocampal CA1 region of Alzheimer's disease model rats, which may partly explain the beneficial effects of TEN on cognitive function.

Key words: Polygala tenuifolia, Saponins, Alzheimer disease, Hippocampus, Brain-derived neurotrophic factor, Receptor protein-tyrosine kinases, Disease models, animal