蔡丽 刘毅 李文涛 陈敏

摘要 目的：研究神經复元方对卒中后抑郁（PSD）模型大鼠脑源性生长因子（BDNF）/酪氨酸激酶受体B（TrkB）表达及海马神经元突触可塑性的影响，探讨其改善抑郁症状的作用机制。方法：采用经典的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，分为假手术组、PSD模型组、氟西汀组、神经复元方低、中、高剂量组。造模成功后干预28 d，比较各组大鼠行为学变化，用荧光定量RT-PCR和蛋白质免疫印迹法检测各组BDNF/TrkB-mRNA及生长相关蛋白-43（GAP-43）及突触素I（SYN I）和突触囊泡素（SYNA）的表达水平，用透射电镜观察海马神经元突触的超微结构。结果：高剂量神经复元方干预后的PSD模型大鼠学习记忆功能提升，海马BDNF和TrkB-mRNA表达比较模型组显著增高，差异有统计学意义（P<0.05），海马神经元突触相关蛋白SYN I和SYNA的表达水平比较模型组明显提高，差异有统计学意义（P<0.05）。高剂量神经复元方组海马神经元突触密度和突触后致密物厚度均显著高于模型组。结论：神经复元方可改善PSD模型大鼠抑郁症状，提升大鼠学习记忆能力，其作用机制可能是通过增加海马BDNF/TrkB的含量，促进海马突触素I和SYNA等突触生长相关蛋白表达，增强PSD模型大鼠海马神经元可塑性而发挥作用。

关键词 神经复元方;卒中后抑郁;脑源性神经营养因子;酪氨酸激酶B;海马;突触可塑性;中医药;实验研究

Effect of Shenjing Fuyuan Decoction on the Expression of BDNF/TrkB and the Synaptic Plasticity of Hippocampal Neurons in PSD Model Rats

CAI Li，LIU Yi，LI Wentao，CHEN Min

（Department of Neurology，Shanghai Municipal Hospital of Traditional Chinese Medicine，Shanghai University of Traditional Chinese Medicine，Shanghai 200071，China）

Abstract Objective：To investigate the effect of Shenjingfuyuan Decoction in regulating BDNF/TrkB signal pathway and the synaptic plasticity of hippocampal neurons in PSD model rats，and to explore its mechanism of improving depression symptoms.Methods：PSD rat model was established by using the classical method of the middle cerebral artery embolism and chronic unforeseeable mild stress combined with solitary nutrition，which were divided into sham-operation group，PSD model group，fluoxetine group，Shenjing Fuyuan Decoction low，middle and high dose group.After 28 days' intervention，the behavioral changes of each group were compared.The expression levels of BDNF/TrkB-mRNA and synapse-related proteins SYN-I，SYNA and GAP-43 were detected by quantitative RT-PCR and immunoblotting.The ultrastructure of hippocampal neuron synapses were observed by transmission electron microscopy.Results：The learning and memory function of PSD model rats was improved after the intervention of high-dose Shenjing Fuyuan Decoction.The expression of BDNF and TrkB gene in hippocampus was significantly higher than that in model group （P<0.01）.The expression of SYN-I and SYNA in hippocampus neurons was significantly higher than that in model group （P<0.01）.The synaptic density and postsynaptic density of hippocampal neurons in the high-dose SD group were significantly higher than those in the model group.Conclusion：Shenjing Fuyuan Decoction can effectively improve the depression of PSD model rats，and improve the learning and memory abilities of rats.Its mechanism may be related to the regulation of BDNF/TrkB signal pathway，promoting the expression of synaptophysin I and SYNA in hippocampus and other synaptic growth-related protein expression，and the enhancement of synaptic plasticity of hippocampal neurons.

Keywords Shenjingfuyuan Decoction; Post-stroke depression; Brain-derived neurotrophic factor; Tyrosine kinase B; Hippocampus; Synaptic plasticity; Traditional Chinese medicine; Experimental study

中图分类号：R285.5文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.04.013

卒中后抑郁（Post-stroke Depression，PSD）是卒中后常见并发症，严重影响患者的神经功能康复和生命质量，导致脑卒中的复发率和死亡率明显增高。据流行病学数据，目前我国PSD发病率为29%～37.9%[1]。对于PSD的治疗近年有很多中药复方表现出良好治疗效果。前期研究证实神经复元方对改善PSD患者抑郁症状有较好疗效[2-3]，但对其作用机制尚无研究。且研究发现脑源性神经营养因子（BDNF）水平与PSD具有相关性。本研究通过建立PSD大鼠模型，予以不同剂量神经复元方干预，并设置对照组比较研究，探讨神经复元方对PSD模型大鼠BDNF/TrkB表达及海马神经元突触可塑性的影响，进而分析改善PSD患者抑郁症状的作用机制。……