L-NAME减少三叉神经脊束核尾侧段和上颈髓后角c-fos和nNOS的表达

目的:进一步研究NO在偏头痛发病机制中的作用,探讨三叉神经血管反射的中枢机制。方法:应用电刺激猫上矢状窦区硬脑膜动物模型,冰冻组织连续切片后行免疫组化染色,分别观察了NOS抑制剂Nω-nitro-L-argi-nine methylester(L-NAME,100mg/kg)对下延髓、上颈髓c-fos蛋白和神经元型NOS(nNOS)表达的影响。结果:c-fos和nNOS阳性神经元主要位于延髓三叉神经脊束核尾侧段和C1后角的浅层(Ⅰ、Ⅱ层),其深层、孤束缝核和中央核、中央导水管两侧可见数个直径较大、轴突较长的nNOS阳性神经元;而nNOS阳性神经纤维遍布后角及中央导水管两侧,并似向前角和后角浅层方向投射,其中后角浅层着色明显比其它部位深。电刺激后可见较长的纤维呈串珠样改变。刺激组动物的c-fos及nNOS阳性神经元数均比假手术对照组明显增加(P<0.01),L-NAME组比刺激组明显减少(P<0.01),而刺激组动物的c-fos及nNOS阳性神经元数与生理盐水组相比均无显著差异(P>0.05)。结论:刺激猫上矢状窦区硬脑膜可激活三叉神经脑干中枢神经元,L-NAME可能通过抑制NO的生成阻断此部位神经元的激活,从而终止偏头痛发作。

c-fos AND nNOS IMMUNOREACTIVITY IN THE TRIGEMINAL NUCLEUS CAUDALIS AND UPPER CERVIC sSPIN AL CORD INDUCED BY ELECTRICAL STIMULATION WERE DECREASED FOLLOWING L-NAME

Objective：To study the central mechanism of trigeminovascular reflex and the role of nitric oxide in migraine attacks.Methods：Effects of Nω-nitro-L-arginine methyl ester（L-NAME） on the expression of c-fos and neuronal nitric oxide synthase（nNOS） immunoreactivity induced by electrical stimulation of the dural mater near the superior sigittal sinus（SSS） were observed in the successive frozed slices of the caudal medulla oblonga and the upper cervical spinal cord of cats.Results：c-fos and nNOS immunoreactive positive neurons were concentrated in the superficial layers（laminae I and II） of the trigeminal nucleus caudalis and the dorsal horn of the C1 segment of the cervical cord,a few larger,axon-elongated nNOS positive cells were observed in the deep layers,the commissural and medial nuclei of the solitary tract and the bilateral area of the central canal;moreover,the nNOS-labelled fibers spreaded over the dorsal horn and the bilateral gray mater of central canal,seemed to project to the ventral,and the supe rificial layers of dorsal horn where the staining is darker than in any other areas.The longer stained-axon became beaded-like after stimulation.c-fos and nNOS immunoreactive positive neurons of the stimulation group increased markedly compared to that of the sham-operated group（P〈0.01）;the positive neuron of the L-NAME group decrease obviously compared to that of the stimulation group（P〈0.01）;but there weren＇t significant difference between the stimulation group and the saline group（P〉0.05）.Conclusion：The brainstem second-order neuron of trigeminal nerve involved in vascular headache could be activated when the cat dura mater near the SSS had been stimulated;L-NAME might block the activation of these neurons by inhibiting NO synthesis,thus abolish acute migraine attacks.