Hiraoka Y, Kishimoto C, Takada H, Nakamura M, Kurokawa M, Ochiai H, Shiraki K
Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
J Am Coll Cardiol. 1996 Nov 15;28(6):1610-5. doi: 10.1016/s0735-1097(96)00372-5.
This study sought to investigate the effects of nitric oxide inhibition in a murine model of coxsackievirus B3 myocarditis.
Little is known about the contribution of nitric oxide to the pathophysiology of myocarditis.
Antiviral activity was tested in vitro using nitric oxide inhibition by treatment with activated macrophages of NG-nitro-L-arginine methyl ester. In the in vivo experiments, NG-nitro-L-arginine methyl ester and NG-nitro-D-arginine methyl ester (both at 100 micrograms/ml) were administered to C3H/He mice early (days 0 to 14) and late (days 14 to 35) after infection with coxsackievirus B3.
In the in vitro experiments with interferon-gamma- and lipopolysaccharide-induced activated murine macrophages, treatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester, but not its inactive enantiomer NG-nitro-D-arginine methyl ester, restored coxsackievirus B3 titers. In the in vivo experiments in the early treatment group, myocardial virus titers were higher in NG-nitro-L-arginine methyl ester-treated than infected untreated animals, and both inflammatory cell infiltration and necrosis were more severe. In the late treatment group, more severe necrosis and more dense myocardial and perivascular fibrosis were observed in NG-nitro-L-arginine methyl ester-treated than in infected untreated animals. NG-Nitro-D-arginine methyl ester administration was ineffective.
Nitric oxide inhibition increases myocardial virus titers, resulting in the aggravation of cardiac pathology in the early stage of coxsackievirus B3 myocarditis. In the late stage, it induces more severe cardiomyopathic lesions. Nitric oxide plays a defensive role in the pathogenesis of coxsackievirus B3 myocarditis.
本研究旨在探讨一氧化氮抑制在柯萨奇病毒B3心肌炎小鼠模型中的作用。
关于一氧化氮在心肌炎病理生理学中的作用知之甚少。
通过用NG-硝基-L-精氨酸甲酯处理活化巨噬细胞以抑制一氧化氮，在体外测试抗病毒活性。在体内实验中，在感染柯萨奇病毒B3后的早期（第0至14天）和晚期（第14至35天），将NG-硝基-L-精氨酸甲酯和NG-硝基-D-精氨酸甲酯（均为100微克/毫升）给予C3H/He小鼠。
在干扰素-γ和脂多糖诱导的活化小鼠巨噬细胞的体外实验中，用一氧化氮合酶抑制剂NG-硝基-L-精氨酸甲酯处理可恢复柯萨奇病毒B3滴度，而其无活性对映体NG-硝基-D-精氨酸甲酯则无效。在早期治疗组的体内实验中，NG-硝基-L-精氨酸甲酯处理的动物心肌病毒滴度高于未处理的感染动物，炎症细胞浸润和坏死都更严重。在晚期治疗组中，与未处理的感染动物相比，NG-硝基-L-精氨酸甲酯处理的动物观察到更严重的坏死以及更致密的心肌和血管周围纤维化。给予NG-硝基-D-精氨酸甲酯无效。
一氧化氮抑制会增加心肌病毒滴度，导致柯萨奇病毒B3心肌炎早期心脏病理加重。在晚期，它会诱发更严重的心肌病病变。一氧化氮在柯萨奇病毒B3心肌炎的发病机制中起防御作用。
