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目的观察吗啡依赖戒断时大鼠脊髓和脑干 μ 受体和κ受体mRNA表达以及毒蕈碱受体拮抗剂、NMDA受体拮抗剂和NOS抑制剂对这些基因表达的影响。方法用逆转录聚合酶链反应(RT -PCR) ,以 β_actinmRNA为内标检测 μ 受体和κ受体mRNA的表达水平。结果吗啡依赖大鼠脊髓和脑干 μ 受体mRNA表达明显升高 ,纳洛酮激发大鼠戒断反应1h后 μ 受体基因表达降低 ,4h后接近正常组,而脊髓和脑干κ受体基因的变化与 μ 受体基因表达趋势相反。鞘内注射PKA抑制剂Rp_cAMPs和蛋白磷酸酶抑制剂calyculinA可以明显减少脊髓和脑干中 μ 受体和κ受体基因表达 ,而PKA激活剂Sp_cAMPs则无明显影响 ;经NOS抑制剂l_N_硝基精氨酸甲酯(l_NAME)处理后 ,脊髓 μ 受体和κ受体基因表达明显减少 ,经毒蕈碱(M)受体拮抗剂甲基东莨菪碱处理后 ,脊髓 μ 受体和脑干κ受体基因表达也明显减少 ,而脊髓κ受体和脑干 μ 受体基因表达变化不明显 ;经NMDA拮抗剂MK801和M1 受体拮抗剂哌拉唑嗪处理后 ,脊髓和脑干 μ 受体和κ受体基因表达较戒断1h组无明显差异。脊髓和脑干中 β_actin基因表达各处理组之间没有差别。结论吗啡依赖和戒断动物脊髓和脑干中 μ 受体和κ受体基因表达发生改变 ,M受体拮抗剂和NOS抑制剂在吗啡戒断反应时减少 μ 受体和κ受体
Objective To investigate the effects of muscarinic receptor antagonist, NMDA receptor antagonist and NOS inhibitor on the expression of μ and κ mRNA in spinal cord and brainstem in morphine dependent withdrawal rats. Methods Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of μ receptor and κ receptor mRNA using β_actin mRNA as an internal standard. Results The mRNA expression of μ receptor in the spinal cord and brainstem of morphine-dependent rats was significantly increased. The expression of μ-receptor gene was decreased after 1 h in naloxone-stimulated withdrawal and close to normal in 4 h, The change of gene is opposite to the trend of μ receptor gene expression. Intrathecal injection of PKA inhibitor Rp_cAMPs and protein phosphatase inhibitor calyculinA can significantly reduce μ and κ receptor gene expression in the spinal cord and brainstem, while PKA activator Sp_cAMPs no significant effect; NOS inhibitor l_N_ nitro L-arginine methyl ester (l_NAME) treatment, spinal cord μ receptor and κ receptor gene expression was significantly reduced by the muscarinic (M) receptor antagonist methyl scopolamine treatment, spinal cord receptor μ and brainstem κ receptor The gene expression of the spinal cord and the brainstem μ receptor gene expression was not significantly changed; the NMDA antagonist MK801 and M1 receptor antagonist piperazolazine treatment, spinal cord and brainstem μ receptor and κ receptor gene expression than withdrawal 1h group no significant difference. There was no difference between the treatment groups for β_actin gene expression in the spinal cord and brainstem. Conclusion The expressions of μ receptor and κ receptor genes were changed in the spinal cord and brainstem of morphine dependent and abstinent animals. M receptor antagonist and NOS inhibitor decreased μ receptor and κ receptor in morphine withdrawal response