Junin virus-induced astrocytosis is impaired by iNOS inhibition
Junin virus-induced astrocytosis is impaired by iNOS inhibition
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DOI：
10.1002/jmv.10254
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发表时间：
2003-01-01
影响因子：
12.7
通讯作者：
Berría, MI
中科院分区：
文献类型：
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作者：
Gómez, RM;Yep, A;Berría, MI
由于小鼠和大鼠的朱宁病毒（JV）实验性脑炎的特征在于轻微的组织病理学变化，这似乎并不证明脑内感染后本身的致死性，这样的小鼠模型似乎足以研究诱导型一氧化氮合酶（iNOS）作为致病因子的潜在作用。伴随着主要的星形胶质细胞反应，在用JV菌株#44感染的小鼠的脑中公开了iNOS、线粒体超氧化物歧化酶（SODm）和谷胱甘肽过氧化物酶（GPX）的免疫过氧化物酶表达增加。当通过腹腔注射氨基胍（AG）实现NOS的特异性抑制时，在治疗动物中观察到显著更高的死亡率（70% vs. 40%），以及相似的感染滴度（类似于10（7）PFU/g），但胶质细胞酸性（GFAP）标记显示星形胶质细胞增多症较低。至于SODm和GPX的免疫化学表达在神经元中，没有发现有或没有AG治疗的小鼠之间的差异。目前的研究结果表明，一氧化氮（NO）的明显的保护作用，当合成的诱导型一氧化氮合酶，是无关的减少病毒复制，而是增强星形胶质细胞活化作为一个有益的细胞反应病毒诱导的中枢神经系统损伤。(C)2003 Wiley-Liss，Inc.
Because Junin virus (JV) experimental encephalitis of mice and rats is characterized by mild histopathological changes that do not seem to justify per se lethality after intracerebral infection, such a murine model seems adequate to investigate the potential role of inducible nitric oxide synthase (iNOS) as a pathogenic factor. Concomitant with a predominant astrocyte reaction, increased immunoperoxidase expression of iNOS, mitochondrial superoxide dismutase (SODm) and glutathione peroxidase (GPX) was disclosed in brain of mice infected with JV strain #44. When specific inhibition of NOS was achieved by intraperitoneal administration of amino guanidine (AG), significantly greater mortality was observed in treated animals (70% vs. 40%), together with similar infective titers (similar to10(7) PFU/g) but lower astrocytosis, as shown by glial fibrillary acidic (GFAP) labeling. As regards SODm and GPX immunochemical expression in neurons, no differences were found between mice with or without AG treatment. The present results suggest that the apparent protective role of nitric oxide (NO), when synthesized by iNOS, is unrelated to reduced viral replication but rather to enhanced astrocyte activation behaving as a beneficial cell response to virus-induced CNS damage. (C) 2003 Wiley-Liss, Inc.