神经复元方对卒中后抑郁大鼠海马神经元雄激素受体表达和活性的影响研究

Study on the effect of Shenjing Fuyuan Decoction on androgen receptor expression and activity of hippocampal neurons in poststroke depression rats

关键词:  神经复元方  卒中后抑郁  雄激素受体  海马神经元  大鼠

Key words:  Shenjing Fuyuan Decoction  post-stroke depression  androgen receptor  hippocampal neurons  rat

摘要:

[目的] 观察神经复元方对卒中后抑郁（PSD）模型大鼠海马神经元雄激素受体（AR）的表达和活性的影响，为探讨其作用机制提供依据。[方法] 采用经典线栓大脑中动脉加用慢性不可预见温和应激结合孤养法，建立PSD大鼠模型，随机分为假手术组、PSD模型组、神经复元方组、氟西汀组。采用糖水偏好实验、旷场实验及Morris水迷宫分时观察大鼠行为学变化，并在药物干预14 d后，采集大鼠海马组织得到神经元细胞，用免疫荧光法和蛋白质免疫印迹法检测细胞中磷酸化AR和非磷酸化AR（p-AR）表达。[结果] 应激第14天，模型组、氟西汀组及神经复元方组糖水消耗量、旷场实验水平与垂直得分较手术前明显降低，模型建立成功。药物干预14 d后，氟西汀组、神经复元方组糖水消耗量、大鼠水平与垂直得分较应激第14天时明显增多，且明显高于模型组；与模型组比较，两组大鼠在Morris水迷宫中定位航行潜伏期缩短，空间搜索时在目标象限的持续时间延长、跨平台次数明显增多；检测细胞中的AR、p-AR阳性表达数与蛋白表达水平，较模型组显著提高。[结论] 神经复元方可改善PSD模型大鼠抑郁症状，提升大鼠的学习记忆能力，其作用机制可能与促进海马神经元AR活化有关。

Abstract:

[Objective] This study aims to investigate the impact of Shenjing Fuyuan Decoction on androgen receptor（AR） expression and activity in rats with post-stroke depression（PSD），and to provide a basis for exploring its mechanism of action. [Methods] The PSD rat model was established by using classical wire bolus to the middle cerebral artery plus chronic unforeseen mild stress combined with the solitary rearing method. Subsequently，the rats were divided into a sham operation group，a PSD model group，a Shenjing Fuyuan group，and a fluoxetine group. A sugar preference test，open field test，and Morris water maze were used to observe the behavioral changes of rats. After 14 days of drug intervention，hippocampal tissue was collected from rats to obtain neuronal cells，and the expression of phosphorylated AR and non-phosphorylated AR（p-AR） in cells was detected using immunofluorescence and protein immunoblotting methods. [Results] On the 14th day of stress，the glucose consumption，and open field test horizontal and vertical scores of the model group，fluoxetine group，and Shenjing Fuyuan group were significantly reduced compared to before surgery，and the model was successfully established. After 14 days of drug intervention，the glucose consumption，horizontal and vertical scores of rats in the fluoxetine group and the Shenjing Fuyuan group significantly increased compared to the 14th day of stress，and were considerably higher than those in the model group. Compared with the model group，the two groups of rats had a shorter latency for navigation in the Morris water maze，a longer duration of spatial search in the target quadrant，and a significant increase in the number of crossings. The expression levels and protein expression levels of AR and p-AR in cells were significantly increased compared to the model group. [Conclusion] Shenjing Fuyuan Decoction improves depressive symptoms and enhances learning memory ability in PSD model rats，and its mechanism of action may be related to the promotion of AR activation.