Effect Of Scutellarin On The Pathway Of Glu/GAGB Metabolism Induced By ?-amyloid Protein In SH-SY5Y Cells

Objective: To observe the effect of scutellarin(Scu)on the key transmitters and proteins of glutamate(Glu)/ gamma aminobutyric acid(GABA)system in the cell model induced by ?-amyloid protein(A?1-42),and to explore the mechanism of scutellarin(Scu)inhibiting the excitotoxicity of Glu induced by A?.Methods: Neuroblastoma cells were divided into control group,A?(1?mol/L)treated group,Scu(10?mol/L)treated group and Scu(10?mol/L)+A?(1?mol/L)treated group.The concentrations of extracellular Glu and GABA in each group was detected by biochemical method and ELISA;The expression of excitatory amino acid transporter 3(EAAT3),GABA transporter 1(GAT-1)and N-methyl-D-aspartate receptor subtype 1(NMDAR1)were detected by Western blot and the m RNA detected by Quantitative Real-time PCR;The contents of total superoxide dismutase(T-SOD)and malondialdehyde(MDA)were measured by xanthine oxidase method and thiobarbituric acid method.Results:(1)There was no statistical difference in the data of each detection index between the control group and the Scu treatment group(P>0.05);(2)Compared with the control group and the Scu treated group,the extracellular Glu was increased and the GABA was decreased in A? treated group,and the differences were statistically significant(p<0.05).Compared with the A? treated group,the extracellular Glu was decreased and the GABA was increased in Scu+A? treated group,and the differences were statistically significant(p<0.05);(3)Compared with the control group and the Scu treated group,the expression of EAAT 3,GAT-1,NMDAR1 protein and m RNA in the cells was increased in A? treated group,and the differences were statistically significant(p<0.05).Compared with the A? treated group,the expression of EAAT 3,GAT-1,NMDAR1 protein and m RNA in the cells was decreased in Scu+A? treated group,and the differences were statistically significant(p<0.05).(4)Compared with the control group and the Scu treated group,the intracellular T-SOD was decreased and the MDA was increased in A? treated group,and the differences were statistically significant(p <0.05).Compared with the A? treated group,the intracellular T-SOD was increased and the MDA was decreased in Scu+A? treated group.Conclusion: Scu may alleviate the Glu excitatory toxicity mediated by A? through antioxidant,improvement of mitochondrial dysfunction,improvement of EAAT3 and GAT-1 transport disorders,and reduction of NMDAR1 expression.