Hiraoka Y, Kishimoto C, Takada H, Kurokawa M, Ochiai H, Shiraki K, Sasayama S
Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Cardiovasc Res. 1993 Jun;27(6):957-61. doi: 10.1093/cvr/27.6.957.
The aim was to test the role of oxygen derived free radicals in the development of myocarditis. This involved investigating the effects of polyethylene glycol conjugated superoxide dismutase (PEG-SOD, an enzyme catalysing the conversion of O2.- to H2O2) and polyethylene glycol conjugated catalase (PEG-catalase, accelerating the reaction of H2O2 to H2O and O2) upon coxsackievirus B3 (CB3) myocarditis.
Two week old male C3H/He mice were inoculated intraperitoneally with 10(3) plaque forming units of CB3. PEG-SOD, 1 x 10(3) U.kg-1 x d-1, and PEG-SOD, 1 x 10(3) U.kg-1 x d-1, plus PEG-catalase, 1 x 10(3) U.kg-1 x d-1, were injected subcutaneously daily on days 0 to 14. Treated groups were compared to the infected control.
On day 7, there were no significant differences in pathological scores among the three groups. On day 14, the cellular infiltration, myocardial necrosis, and calcification scores were significantly lower in the PEG-SOD group and the PEG-SOD plus PEG-catalase group than in the control. There were no significant differences in pathological scores between the PEG-SOD group and the PEG-SOD plus PEG-catalase group. There were no differences in the myocardial virus titres on day 7 among the three groups. On day 14, virus was not detected from the myocardium in any of the three groups.
The results suggest that superoxide anion is mostly responsible for myocyte injury in CB3 myocarditis in mice, and that hydrogen peroxide formed as a result of dismutation of superoxide anion may not play a significant role in the development of myocarditis. Superoxide anion is one of the most important factors in free radical mediated injury in CB3 myocarditis in mice and the administration of PEG-SOD alone has therapeutic potential in clinical CB3 myocarditis.
旨在测试氧衍生自由基在心肌炎发展过程中的作用。这涉及研究聚乙二醇共轭超氧化物歧化酶(PEG-SOD,一种催化O2.-转化为H2O2的酶)和聚乙二醇共轭过氧化氢酶(PEG-过氧化氢酶,加速H2O2转化为H2O和O2的反应)对柯萨奇病毒B3(CB3)心肌炎的影响。
将两周龄雄性C3H/He小鼠腹腔内接种10(3)个噬斑形成单位的CB3。在第0至14天,每天皮下注射PEG-SOD,1×10(3) U.kg-1×d-1,以及PEG-SOD,1×10(3) U.kg-1×d-1加PEG-过氧化氢酶,1×10(3) U.kg-1×d-1。将治疗组与感染对照组进行比较。
在第7天,三组之间的病理评分无显著差异。在第14天,PEG-SOD组和PEG-SOD加PEG-过氧化氢酶组的细胞浸润、心肌坏死和钙化评分显著低于对照组。PEG-SOD组和PEG-SOD加PEG-过氧化氢酶组之间的病理评分无显著差异。在第7天,三组之间的心肌病毒滴度无差异。在第14天,三组中任何一组的心肌均未检测到病毒。
结果表明,超氧阴离子在小鼠CB3心肌炎中主要负责心肌细胞损伤,并且超氧阴离子歧化产生的过氧化氢在心肌炎发展中可能不发挥重要作用。超氧阴离子是小鼠CB3心肌炎自由基介导损伤的最重要因素之一,单独给予PEG-SOD在临床CB3心肌炎中具有治疗潜力。