Oyanagui Y, Sato S
Drug Development Laboratories of Fujisawa Pharmaceutical Co., Osaka, Japan.
Free Radic Res Commun. 1991;12-13 Pt 1:229-37. doi: 10.3109/10715769109145791.
Carrageenan-induced paw edemata of mice and rats were suppressed by 1-4 x 10(3) U/kg intravenous injection of heparin. High doses were less suppressive, corresponding well to the increase in plasma SOD activity. This biphasic dose response curve was also observed in our ischemic paw model of mice. Increased SOD appeared as high molecular EC-SOD C (in mice) and B (in rats) as a result of its sensitivity to a copper chelator and long retention time in the blood stream, compared to the short life of cytosolic Cu, Zn-SOD. EC-SOD C (135 kDa) failed to be detected in the plasma of heparin-injected mice by way of nitroblue tetrazolium staining after PAGE electrophoresis. Instead, SOD activity was found near 270 kDa. An excess heparin-loaded subunit of this enzyme might become inactivated or might not be able to fix to a pocket where EC-SOD eliminates O2-, to protect the endothelium, Electrophoresis dissociates the excess heparin resulting in an active form of the enzyme. Paw edemata of rats were less sensitive because this species lacks the strongly heparin-binding EC-SOD C and has only the weakly heparin-binding EC-SOD B, Ischemia-induced mitochondrial swelling of the paw muscle was observed by electron microscopy and was prevented by heparin injection.
静脉注射1-4×10(3)U/kg肝素可抑制角叉菜胶诱导的小鼠和大鼠爪部水肿。高剂量的抑制作用较弱，这与血浆超氧化物歧化酶（SOD）活性的增加情况相符。在我们的小鼠缺血爪模型中也观察到了这种双相剂量反应曲线。由于与胞质铜锌超氧化物歧化酶（Cu, Zn-SOD）的短寿命相比，其对铜螯合剂敏感且在血流中保留时间长，因此增加的SOD以高分子量的细胞外超氧化物歧化酶C（在小鼠中）和B（在大鼠中）的形式出现。通过聚丙烯酰胺凝胶电泳（PAGE）后的硝基蓝四氮唑染色法，在注射肝素的小鼠血浆中未检测到细胞外超氧化物歧化酶C（135 kDa）。相反，在270 kDa附近发现了超氧化物歧化酶活性。该酶过量负载肝素的亚基可能会失活，或者可能无法固定在细胞外超氧化物歧化酶消除超氧阴离子以保护内皮的口袋中。电泳会使过量的肝素解离，从而产生该酶的活性形式。大鼠的爪部水肿不太敏感，因为该物种缺乏与肝素结合力强的细胞外超氧化物歧化酶C，仅具有与肝素结合力弱的细胞外超氧化物歧化酶B。通过电子显微镜观察到缺血诱导的爪部肌肉线粒体肿胀，肝素注射可预防这种肿胀。
