Ding M, Zhang M, Wong J L, Rogers N E, Ignarro L J, Voskuhl R R
Department of Neurology, UCLA School of Medicine, Los Angeles, CA 90095, USA.
J Immunol. 1998 Mar 15;160(6):2560-4.
We used an antisense oligodeoxynucleotide (ODN) complementary to inducible nitric oxide synthase (iNOS) to inhibit experimental autoimmune encephalomyelitis (EAE) in female SJL/J mice, an animal model for multiple sclerosis. The antisense ODN was administered intraventricularly to mice daily for 10 days beginning at the time of adoptive transfer of myelin basic protein-specific T lymphocytes. The antisense ODN treatment significantly reduced the clinical score of EAE and blocked iNOS mRNA and protein synthesis, as well as iNOS enzyme activity within the central nervous system. The levels of nitric oxide and cyclic guanosine monophosphate were also significantly reduced by the antisense ODN treatment. Neither sense nor random ODN affected clinical EAE or iNOS expression. Moreover, the protein and enzyme activity level of constitutive neuronal nitric oxide synthase was not affected by the antisense ODN. Thus, we have shown that the iNOS antisense ODN specifically blocked iNOS expression and ameliorated the induction of EAE.
我们使用了一种与诱导型一氧化氮合酶（iNOS）互补的反义寡脱氧核苷酸（ODN）来抑制雌性SJL/J小鼠的实验性自身免疫性脑脊髓炎（EAE），这是一种多发性硬化症的动物模型。从髓鞘碱性蛋白特异性T淋巴细胞过继转移时开始，每天向小鼠脑室内注射反义ODN，持续10天。反义ODN治疗显著降低了EAE的临床评分，并阻断了中枢神经系统内iNOS mRNA和蛋白质的合成以及iNOS酶活性。反义ODN治疗还显著降低了一氧化氮和环磷酸鸟苷的水平。正义ODN和随机ODN均未影响EAE的临床症状或iNOS的表达。此外，组成型神经元一氧化氮合酶的蛋白质和酶活性水平不受反义ODN的影响。因此，我们已经证明iNOS反义ODN特异性地阻断了iNOS的表达，并改善了EAE的诱导。
