GAT-1下调对氧化槐定碱镇痛作用的影响

Effect of down-regulation of GAT-1 on analgesic action of oxysophoridine

目的:研究中枢GAT-1下调对氧化槐定碱(oxysophoridine,OSR)镇痛作用的影响。方法:采用热板法观察并分析γ-氨基丁酸(gamma aminobutyric acid,GABA)及GABA运载蛋白(GABA transporter 1,GAT-1)抑制剂NO-711与OSR镇痛的协同作用;采用Real time RT-PCR方法检测OSR对福尔马林致痛小鼠脊髓和大脑GAT-1 mRNA表达的影响,分析中枢GAT-1的变化对OSR镇痛作用的影响。结果:GABA(2.0 mg.kg-1,icv)和NO-711(0.125 mg.kg-1,icv)均可显著加强阈下镇痛剂量OSR(32.0 mg.kg-1,iv)在小鼠热板反应中的镇痛作用,使小鼠痛阈明显提高(P<0.05,P<0.01);OSR(500.0 mg.kg-1,iv)可明显抑制福尔马林致痛小鼠脊髓和大脑GAT-1 mRNA的表达(P<0.05,P<0.01)。结论:中枢GAT-1参与了OSR的镇痛作用,GAT-1基因下调能增强OSR的镇痛作用。

Objective： To study the effect of GABA transporter（GAT-1）on the analgesic action of oxysophoridine（OSR） in the central nervous system of mice. Method： Hot plate test was used to observe and analyze the effect of gamma aminobutyric acid and the inhibitor of GAT-1 （NO-711） on the analgesic action of oxysophoridine. Real time RT-PCR was used to investigate the influence of OSR on the expression of GAT-1 mRNA induced by formalin in spinal cord and brain of mice. Result： Both GABA （2.0 mg·kg^-1,icv） and NO-711（0.125 mg·kg^-1,icv） enhanced the analgesic action of OSR （32.0 mg·kg^-1,iv） in the hot plate test, and the latencies was markedly increased （P〈0.05,P〈0.01）. OSR （500.0 mg·kg^-1,iv） significantly inhibited the expression of GAT-1 mRNA induced by formalin（P〈0.05）. Conclusion： GAT-1 was involved in the analgesia effect of OSR and the down^-regulation of GAT-1 mRNA enhanced the analgesic effect.