【作者】 李其；

【导师】 洪炎国；

【作者基本信息】 福建师范大学 ， 动物学， 2008， 硕士

【摘要】 本实验主要是对连续激活SNSR受体(sensory neuron-specific receptor)后降低吗啡镇痛效力及其机制的研究。疼痛行为学和免疫组织化学实验表明,连续鞘内注射SNSR的特异性激动剂BAM8-22(bovine adrenal medulla peptide8-22)后,降低吗啡在福尔马林模型中的镇痛作用。随后我们研究了NMDA受体(N-methyl-D-aspartate receptors)在其中参与的作用,和连续激活SNSR后引起吗啡作用效果下降的分子机制。目前的研究结果为:连续6天鞘内注射BAM8-22 10 nmol,吗啡不能抑制由福尔马林诱发的疼痛行为,并且脊髓中c-Fos表达和NADPH-d阳性神经元数目都明显增加。而联合注射BAM8-22和NMDA受体的拮抗剂AP-5抑制了上述实验现象,吗啡保持其镇痛效力。另外,我们发现连续注射BAM8-22会诱导在脊髓中的NADPH-d和DRG(dorsal root ganglia)中CGRP(Calcitonin-gene-related peptide)表达增加。实验结果表明,连续激活SNSR可以引起吗啡镇痛作用的下降,这一过程是通过激活NMDA受体来介导的。可能的机制是由于连续激活SNSR引起脊髓中一氧化氮(nitric oxide,NO)信号通路的激活和DRG中的CGRP合成或释放的增加,进一步影响NMDA受体信号通路从而引起吗啡镇痛效力的下降。更多还原

【Abstract】 The present studies were designed to investigate that the effects of consecutive activation of sensory neuron-specific receptor(SNSR)on potency of morphine antinociception and its mechanisms.The experiment first demonstrated that consecutive activation of SNSR by intrathecal(i.t.)administration of the specific agonist of SNSR BAM8-22 on potency of morphine antinociception which was revealed by the effects of morphin in formalin test.Then, we examined the hypothesis that activation of NMDA may be involved the effects of activation of SNSR on morphine’s action.Lastly,we investigated molecul mechanisms.The present studies showed that following daily administration of BAM8-22 at a dose of 10 nmol for 6 days,i.t.morphine did not inhibit formalin-evoked nocifensive behaviours, expression of c-fos and NADPH-d neurons in the spinal cord and these responses were reversed by co-administration of AP-5,an NMDA receptor antagonist,with BAM8-22.Furthermore, chronic BAM8-22 induced significant increases in NADPH-d-positive neurons in the spinal cord and CGRP(Calcitonin-gene-related peptide)in dorsal root ganglia(DRG).The results in the current studies indicate that consective pharmacological stimulation of SNSR caused pontency of morphine antinociceptive,and this response was mediated via activation of NMDA receptors.Activation of NOS signal pathway in the spinal cord and increase of CGRP synthesis or/and release of CGRP in DRG underlined NMDA-mediated effects of activation of SNSR.更多还原