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Objective:To investigate the relationship between the excitotoxicity and seruminducible kinase(SNK)and spine-associated Rap GTPase-activating protein(SPAR)pathway in primary hippocampal neuron injury induced by glutamate and furthermore,to explore the molecular between ZBPYR and the morphological regulation of dendritic spines.Methods:The serum containing ZBPYR was prepared by seropharmacology.Reverse transcription and polymerase chain reaction(RT-PCR)was used to detect the expression of mRNA for SNK,SPAR,postsynaptic density protein 95(PSD-95)and N-methyl-D-aspartate(NMDA)receptor subunits(NR1,NR2A and NR2B)in primary rat hippocampal neuron cultures after pretreatment with 10 μ mol/L glutamate and ZBPYR serum.Results:ZBPYR serum pretreatment resulted in a significant down-regulation of glutamate-induced SNK mRNA expression(P<0.05).Significant up-regulation was seen on the mRNA expression of SPAR and PSD-95 (P<0.05).All these changes were dose-dependent.The mRNA expression of NR1,NR2A and NR2B was down-regulated to different degrees(P<0.05).Conclusion:The mechanism of effect of ZBPYR on glutamate-induced excitotoxicity may be related to the regulation of SNK-SPAR signal pathway.ZBPYR may play a role in protecting and maintaining the normal morphology and structure of dendritic spines,which may be achieved by inhibiting the excessive activation of NMDA receptors.