Zielasek J, Jung S, Gold R, Liew F Y, Toyka K V, Hartung H P
Department of Neurology, Julius-Maximilians-Universität, Würzburg, Germany.
J Neuroimmunol. 1995 Apr;58(1):81-8. doi: 10.1016/0165-5728(94)00192-q.
The nitric oxide (NO) synthase pathway is activated during experimental autoimmune inflammation of the central nervous system, and administration of aminoguanidine, an inhibitor of the cytokine-inducible NO synthase (NOS), ameliorated the disease course of autoimmune encephalomyelitis in the SJL mouse. We studied the role of nitric oxide synthase (NOS) in the pathogenesis of experimental autoimmune neuritis (EAN) and experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. NG-L-monomethyl-arginine (L-NMMA), a competitive inhibitor of NOS, partially suppressed T cell line-mediated EAN, but not myelin-induced EAN, myelin basic protein (MBP)-induced EAE, or T cell line-mediated EAE. Aminoguanidine (AG), a selective inhibitor of the cytokine-inducible NOS, enhanced MBP-induced EAE, but had no significant effects on myelin-induced EAN. Two other NOS inhibitors, nitro-arginine methyl-ester and N-nitro arginine, had only little or no effects in EAN and EAE. The administration of NOS inhibitors showed some striking effects in EAN and EAE, but the observed diversity of actions points to a much more complex role of the NO pathway than previously suggested.
在中枢神经系统的实验性自身免疫炎症过程中，一氧化氮（NO）合酶途径被激活，而细胞因子诱导型NO合酶（NOS）的抑制剂氨基胍的给药改善了SJL小鼠自身免疫性脑脊髓炎的病程。我们研究了一氧化氮合酶（NOS）在Lewis大鼠实验性自身免疫性神经炎（EAN）和实验性自身免疫性脑脊髓炎（EAE）发病机制中的作用。NOS的竞争性抑制剂NG-L-单甲基精氨酸（L-NMMA）部分抑制了T细胞系介导的EAN，但对髓鞘诱导的EAN、髓鞘碱性蛋白（MBP）诱导的EAE或T细胞系介导的EAE没有抑制作用。细胞因子诱导型NOS的选择性抑制剂氨基胍（AG）增强了MBP诱导的EAE，但对髓鞘诱导的EAN没有显著影响。另外两种NOS抑制剂，硝基精氨酸甲酯和N-硝基精氨酸，对EAN和EAE只有很小的影响或没有影响。NOS抑制剂的给药在EAN和EAE中显示出一些显著的作用，但观察到的作用多样性表明NO途径的作用比以前认为的要复杂得多。
