内源性大麻素类似物NAGly对大鼠脊髓胶状质神经元的突触传递的抑制作用

The effects of endocannabinoid analogue NAGly on synaptic transmission in spinal substantia gelatinosa of rats

目的探讨内源性大麻素类似物N-花生四烯酰甘氨酸（N-arachidonylglycine，NAGly）对脊髓后角II层胶状质（SG）神经元突触兴奋性的影响。方法：选用生后4—6周雄性SD大鼠，深麻醉后蔗糖人工脑脊液快速心脏灌注处死，取脊髓腰膨大段，制备保留脊髓腰膨大处一侧后根的脊髓矢状切片。利用膜片钳技术，对脊髓后角II层SG神经元进行全细胞记录，通过分析后根刺激诱发的兴奋性突触后电流（eEPSC）的变化情况，观察NAGly（20μmol／L）对SG神经元突触传递兴奋性的影响，以及对自发性兴奋性突触后电流（sEPSC）的发放频率及幅度的影响。结果：通过诱发刺激的强度、潜伏期以及纤维传导速度我们将记录到的SG神经元分为A8纤维／C纤维投射神经元，NAGly对Aδ纤维和C纤维介导的eEPSC的幅度都有明显的抑制作用（P〈0．001），并且这种作用可以被洗脱。NAGly对sG神经元的SEPSC的频率有明显的抑制，但不明显改变其幅度，提示其作用部位在突触前。结论：内源性大麻素类似物NAGly可以抑制脊髓后角浅层Aδ纤维及C纤维介导的突触传递，并通过突触前机制抑制SG神经元的兴奋性。提示内源性大麻素类似物NAGly可通过抑制伤害性C和A纤维介导的突触传递发挥镇痛作用。

Objective： To determine the effects of endocannabinoid analogue NAGly （N-araehidonylglyeine）on excitatory synaptic transmission of substantia gelatinosa （ SG ） neurons and the spontaneous excitability of SG neurons in the spinal dorsal horn of rats. Methods： Male Sprague-Dawley rats （4 -6 weeks old） were anaesthetized and killed by heart perfusion of sucrose artificial eerebrospinal fluid. Quickly cut out the lumbosaeral enlargement of the spinal cord and cut sagittal spinal cord slices with a single dorsal root attached. Whole-cell, voltage-clamp recordings were made in SG neurons to investigate the effect of NAGly （20 μmol/l ） on dorsal root stimulation evoked excitatory postsynaptie currents （eEPSCs） and spontaneous EPSC （sEPSC）. Results： SG neurons were primarily divided into Aδ and C fiber inputting neurons by differentiate their inducing intensity of the electric stimulation, latency and conductive velocity of the fibers. NAGly significantly inhibits the peak amplitude of monosynaptic eEPSCs mediated by primary Aδ and C fibers （P 〈 0.001 ） , which were reversible by washing out. The frequency of sEPSCs was significantly inhibited by the superfusion of NAGly, while the amplitude of sEPSCs was not affected, which suggest the acting site of NAGly is presynaptie. Conclusion： The endocannabinoid analogue NAGly may attenuate nociceptive transmission in spinal dorsal horn through inhibi- ting excitatory synaptic transmission of SG neurons mediated by primary C and Aδ fibers.