Shin T, Tanuma N, Kim S, Jin J, Moon C, Kim K, Kohyama K, Matsumoto Y, Hyun B
Department of Veterinary Medicine, Cheju National University, South Korea.
J Neuroimmunol. 1998 Dec 1;92(1-2):133-8. doi: 10.1016/s0165-5728(98)00194-5.
We studied the effect of nitric oxide (NO) on experimental autoimmune myocarditis (EAC) in rats. We examined the role of inducible nitric oxide synthase (iNOS), an enzyme that produces NO, on hearts affected with EAC, by testing the effects of aminoguanidine (AG), a selective iNOS inhibitor, on the course of EAC. Western blotting detected iNOS in the affected cardiac tissues, but not in CFA immunized cases. Immunohistochemically, the majority of ED1+ macrophages in the EAC lesions were positive for iNOS and nitrotyrosine. A high dose of AG (200 mg/kg/day) significantly reduced the incidence of EAC (p < 0.05) and ameliorated the histological score for the cardiac inflammation (p < 0.01) compared with the low dose AG (100 mg/kg/day) and vehicle treated groups. The immunoblot analysis showed that a high dose of AG effectively suppressed iNOS in hearts affected with EAC. An iNOS band was barely detected in the high dose AG (200 mg/kg) treated group, while it was distinctively visualized in the vehicle and low dose AG (100 mg/kg) treated groups. These results suggest that iNOS is upregulated in EAC lesions and increased NO production plays an important role in the development of EAC. In addition, selective iNOS inhibitors may have a therapeutic role in treating certain autoimmune diseases including EAC.
我们研究了一氧化氮（NO）对大鼠实验性自身免疫性心肌炎（EAC）的影响。我们通过测试选择性诱导型一氧化氮合酶（iNOS）抑制剂氨基胍（AG）对EAC病程的影响，来研究产生NO的酶iNOS在受EAC影响的心脏中的作用。蛋白质免疫印迹法在受影响的心脏组织中检测到了iNOS，但在接受弗氏完全佐剂（CFA）免疫的病例中未检测到。免疫组织化学显示，EAC病变中大多数ED1+巨噬细胞iNOS和硝基酪氨酸呈阳性。与低剂量AG（100mg/kg/天）和赋形剂处理组相比，高剂量AG（200mg/kg/天）显著降低了EAC的发病率（p<0.05），并改善了心脏炎症的组织学评分（p<0.01）。免疫印迹分析表明，高剂量AG有效抑制了受EAC影响心脏中的iNOS。在高剂量AG（200mg/kg）处理组中几乎检测不到iNOS条带，而在赋形剂和低剂量AG（100mg/kg）处理组中则明显可见。这些结果表明，iNOS在EAC病变中上调，NO生成增加在EAC的发展中起重要作用。此外，选择性iNOS抑制剂可能在治疗包括EAC在内的某些自身免疫性疾病中具有治疗作用。
