聚乙二醇共轭超氧化物歧化酶对小鼠柯萨奇病毒B3心肌炎的影响。
Effects of polyethylene glycol conjugated superoxide dismutase on coxsackievirus B3 myocarditis in mice.
作者信息
Hiraoka Y, Kishimoto C, Kurokawa M, Ochiai H, Sasayama S
机构信息
Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
出版信息
Cardiovasc Res. 1992 Oct;26(10):956-61. doi: 10.1093/cvr/26.10.956.
OBJECTIVE
The aim was to examine the role of oxygen derived free radicals in the development of myocarditis by investigating the effects of polyethylene glycol conjugated superoxide dismutase (PEG-SOD), a potent scavenger of oxygen free radicals, upon coxsackievirus B3 (CB3) myocarditis.
METHODS
Two week old male C3H/He mice were inoculated intraperitoneally with 10(3) plaque forming units of CB3. PEG-SOD, 1 x 10(3), 5 x 10(3), 1 x 10(4), and 1 x 10(5) U.kg-1 x d-1, was given subcutaneously daily on days 0 to 14. Treated groups were compared to the infected control.
RESULTS
The survival rate of the 1 x 10(5) U.kg-1 x d-1 PEG-SOD group was lower than that of the infected control group (40% v 78%, p < 0.01). The survival rates of the other treated groups did not differ significantly from the infected control. The myocardial calcification score in the 1 x 10(5) U.kg-1 x d-1 PEG-SOD group was higher than in the infected control group on d 7, when myocardial virus titres did not differ significantly among the five groups. The scores for myocardial cellular infiltration and myocardial necrosis in the 1 x 10(3) and the 5 x 10(3) U.kg-1 x d-1 PEG-SOD groups were significantly lower than in the infected control on d 14, when myocardial viruses were not detected in the five groups. However, the myocardial necrosis and myocardial calcification scores in the 1 x 10(5) U.kg-1 x d-1 PEG-SOD group were higher than in the infected control.
CONCLUSIONS
The improvement of cardiac pathology in the 1 x 10(3) and the 5 x 10(3) U.kg-1 x d-1 PEG-SOD groups seems to have resulted not from the reduction in myocardial virus titres but from inhibition of generation of oxygen free radicals. The mechanism of the impaired survival and aggravation of cardiac pathology in the 1 x 10(5) U.kg-1 x d-1 PEG-SOD group is unknown. The results suggest that oxygen free radicals may be involved in the pathogenesis and development of CB3 myocarditis and that appropriate dosages of PEG-SOD have therapeutic potential for clinical CB3 myocarditis, although caution must be paid to the treatment window.
目的
通过研究聚乙二醇结合超氧化物歧化酶（PEG-SOD）（一种有效的氧自由基清除剂）对柯萨奇病毒B3（CB3）心肌炎的影响，来探讨氧衍生自由基在心肌炎发展过程中的作用。
方法
给两周大的雄性C3H/He小鼠腹腔注射10³空斑形成单位的CB3。在第0至14天，每天皮下给予1×10³、5×10³、1×10⁴和1×10⁵ U·kg⁻¹·d⁻¹的PEG-SOD。将治疗组与感染对照组进行比较。
结果
1×10⁵ U·kg⁻¹·d⁻¹ PEG-SOD组的存活率低于感染对照组（40%对78%，p<0.01）。其他治疗组的存活率与感染对照组无显著差异。在第7天，1×10⁵ U·kg⁻¹·d⁻¹ PEG-SOD组的心肌钙化评分高于感染对照组，此时五组之间的心肌病毒滴度无显著差异。在第14天，当五组中均未检测到心肌病毒时，1×10³和5×10³ U·kg⁻¹·d⁻¹ PEG-SOD组的心肌细胞浸润和心肌坏死评分显著低于感染对照组。然而，1×10⁵ U·kg⁻¹·d⁻¹ PEG-SOD组的心肌坏死和心肌钙化评分高于感染对照组。
结论
1×10³和5×10³ U·kg⁻¹·d⁻¹ PEG-SOD组心脏病理状况的改善似乎并非源于心肌病毒滴度的降低，而是源于对氧自由基生成的抑制。1×10⁵ U·kg⁻¹·d⁻¹ PEG-SOD组存活率受损和心脏病理状况加重的机制尚不清楚。结果表明，氧自由基可能参与了CB3心肌炎的发病机制和发展过程，适当剂量的PEG-SOD对临床CB3心肌炎具有治疗潜力，尽管必须注意治疗窗。
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