福建中医药2025,Vol.56Issue(1):17-21,29,6.DOI:10.13260/j.cnki.jfjtcm.2025.01005
基于NMDAR1-PSD-nNOS通路探讨栝楼桂枝颗粒对神经元兴奋性毒性损伤后突触可塑性的影响
Effect of Gualou Guizhi Granule on Synaptic Plasticity after Neuronal Excitotoxic Injury Based on NMDAR1-PSD-nNOS Pathway
摘要
Abstract
Objective:To study the effect of Gualou Guizhi Granule(GLGZG)on synaptic plasticity after neuronal excitotoxicity injury based on the NMDAR1-PSD-nNOS pathway,and to provide an experimental basis for the treatment of ischemic stroke with GLGZG.Methods:Primary hippocampal neurons were isolated from newborn rats and divided into control group,model group,low-dose group,and medium-dose group.An N-methyl-D-aspartate(NMDA)-induced neuronal excitotoxic injury model was established.The control group was cultured in complete medium without NMDA.The model group was induced with complete medium contain-ing 200 μmol/L NMDA for 6 hours.The low and medium-dose groups were intervened with complete medium containing 100 and 200 μg/mL GLGZG solution,respectively,for 24 hours before being exposed to 200 μmol/L NMDA for 6 hours.After intervention,neuronal morphology was observed using an electron microscope.Neuronal survival rate was detected by the MTT assay,lactate dehy-drogenase(LDH)levels were measured using the LDH method,and the transcription levels of NeuN,GAP-43,PSD-95,and NM-DAR1 mRNA in neurons were detected by qPCR.The relative expression levels of NeuN,GAP-43,PSD-95,MAP-2,Synapsin-1,NMDAR1,and nNOS proteins were detected by Western blot.Results:Compared with the control group,neuronal morphology of the model group was abnormal,neuronal survival rate and transcription levels of NeuN,GAP-43,PSD-95,and NMDAR1 mRNA decreased,as well as relative expression levels of NeuN,GAP-43,PSD-95,MAP-2,Synapsin-1,NMDAR1,and nNOS proteins(P<0.05),but LDH level increased(P<0.05).Compared with the model group,the low and medium-dose groups showed significant im-provement in neuronal morphology and neuronal survival rate increased,with LDH levels reducing(P<0.05).The transcription levels of NeuN and NMDAR1 mRNA,as well as the relative expression levels of NeuN,GAP-43,PSD-95,and Synapsin-1 proteins,were increased in the low-dose group(P<0.05).In the medium-dose group,the transcription levels of NeuN,GAP-43,PSD-95,and NM-DAR1 mRNA,as well as the relative expression levels of NeuN,GAP-43,PSD-95,Synapsin-1,MAP-2,NMDAR1,and nNOS pro-teins all increased(P<0.05).Compared with the low-dose group,the LDH level and the relative expression levels of MAP-2 and Syn-apsin-1 proteins increased in the medium-dose group(P<0.05).Conclusion:GLGZG can reduce NMDA-induced neuronal excitotox-ic injury,which may be related to promoting neuronal synaptic plasticity by regulating the NMDAR1-PSD-nNOS pathway.关键词
神经元损伤/脑卒中/神经可塑性/栝楼桂枝颗粒Key words
neuronal injury/stroke/neural plasticity/Gualou Guizhi Granule引用本文复制引用
冯怡,李雪珍,李亚男,陈雯婷,罗书萍,张玉琴..基于NMDAR1-PSD-nNOS通路探讨栝楼桂枝颗粒对神经元兴奋性毒性损伤后突触可塑性的影响[J].福建中医药,2025,56(1):17-21,29,6.基金项目
国家自然科学基金项目(81803768) (81803768)
福建省自然科学基金面上项目(2024J01127) (2024J01127)
福建中医药大学基础类学科科研提升计划项目(XJC2022009) (XJC2022009)