Hiraoka Y, Kishimoto C, Takada H, Suzaki N, Shiraki K
Second Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Eur Heart J. 1995 Dec;16(12):1900-6. doi: 10.1093/oxfordjournals.eurheartj.a060845.
Granulocyte colony-stimulating factor is a potent activator of mature granulocytes, and subsequently enhances superoxide release. The purpose of this study was to investigate the effects of granulocyte colony-stimulating factor upon murine coxsackievirus B3 myocarditis in relation to free radical-mediated cardiac damage. Two-week-old, male, C3H/He mice were inoculated intraperitoneally with coxsackievirus B3. Granulocyte colony-stimulating factor 20 micrograms.kg-1.day-1, polyethylene glycol-conjugated superoxide dismutase (an enzyme catalyzing the conversion of O2- to H2(O2)) 1 x 10(3) U.kg-1.day-1 and granulocyte colony-stimulating factor 20 micrograms.kg-1.day-1, plus polyethylene glycol-conjugated superoxide dismutase 1 x 10(3) U. kg-1. day-1, were injected subcutaneously daily on days 0 to 14. Treated groups were compared to the infected, untreated group. The survival rate in the polyethylene glycol-conjugated superoxide dismutase group was higher than that of the untreated group on day 14, but on day 7, cardiac pathology was not significantly different among the four groups. On day 14, the scores of cellular infiltration, myocardial necrosis and calcification were lower in the polyethylene glycol-conjugated superoxide dismutase group and in the granulocyte colony-stimulating factor plus polyethylene glycol-conjugated superoxide dismutase group than in the untreated group. The myocardial virus titres on days 7 and 14 did not differ significantly among the four groups. The number of total white blood cell and neutrophil counts were significantly greater in the granulocyte colony-stimulating factor group than in the untreated group on day 7. Taken altogether with the previous reports and present evidence that the administration of granulocyte colony-stimulating factor did not exacerbate coxsackievirus B3 myocarditis, it may be that oxygen-free radicals appeared to be derived not from leukocytes but from other components in this experimental model of myocarditis, whereas the myocardium was inflamed with leukocytes.
粒细胞集落刺激因子是成熟粒细胞的强效激活剂，随后可增强超氧化物的释放。本研究的目的是探讨粒细胞集落刺激因子对小鼠柯萨奇病毒B3心肌炎的影响，以及与自由基介导的心脏损伤的关系。将两周龄雄性C3H/He小鼠腹腔接种柯萨奇病毒B3。在第0至14天，每天皮下注射粒细胞集落刺激因子20微克·千克⁻¹·天⁻¹、聚乙二醇共轭超氧化物歧化酶（一种催化O₂⁻转化为H₂O₂的酶）1×10³单位·千克⁻¹·天⁻¹，以及粒细胞集落刺激因子20微克·千克⁻¹·天⁻¹加聚乙二醇共轭超氧化物歧化酶1×10³单位·千克⁻¹·天⁻¹。将治疗组与感染未治疗组进行比较。在第14天，聚乙二醇共轭超氧化物歧化酶组的存活率高于未治疗组，但在第7天，四组之间的心脏病理学无显著差异。在第14天，聚乙二醇共轭超氧化物歧化酶组以及粒细胞集落刺激因子加聚乙二醇共轭超氧化物歧化酶组的细胞浸润、心肌坏死和钙化评分低于未治疗组。在第7天和第14天，四组之间的心肌病毒滴度无显著差异。在第7天，粒细胞集落刺激因子组的白细胞总数和中性粒细胞计数显著高于未治疗组。综合先前的报道和目前的证据，即给予粒细胞集落刺激因子并未加重柯萨奇病毒B3心肌炎，在这个心肌炎实验模型中，氧自由基似乎并非来自白细胞，而是来自其他成分，尽管心肌是由白细胞引发炎症。
