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Uptake of I-125-PDGF-AB to the blood after extravascular administration in mice

机译:小鼠血管外给药后I-125-PDGF-AB对血液的吸收

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The kinetics of exogenously given I-125-platelet-derived growth factor-AB (PDGF-AB) was studied in mice. I-125-PDGF-AB was injected either intraperitoneally, intramuscularly or subcutaneously and the resulting concentrations of I-125-radioactivity monitored in the blood at different times. The serum levels of I-125-radioactivity rose to a maximum 2-4 hours after injection, before decreasing. Precipitation of serum with trichloroacetic acid demonstrated that 50 per cent or more of the I-125 remained in macromolecular form. Further, gel chromatography studies showed that the molecular size of the labelled material in serum, three hours after injection, was the same as that of the original I-125-PDGF-AB. In addition, a low-molecular weight fraction was observed, indicating the presence of degradation products. The largest proportion of degraded material was obtained after subcutaneous administration. The absence of partially degraded I-125-labelled fragments, e.g. I-125 oligopeptides, indicates complete rather than limited degradation and suggests that the I-125-PDGF-AB had been processed by cellular uptake. It is concluded that extra-vascularly given PDGF-AB in mice is taken up into the blood in intact macromolecular form. This finding suggests that it is possible to administer PDGF extravascularly to obtain a prolonged increase in the concentration of intact PDGF in the blood. [References: 25]
机译:在小鼠中研究了外源给予I-125-血小板衍生的生长因子-AB(PDGF-AB)的动力学。腹膜内,肌内或皮下注射I-125-PDGF-AB,并在不同时间监测血液中I-125放射性的浓度。注射后血清I-125放射性水平上升到最大2-4小时,然后才下降。用三氯乙酸沉淀血清表明,I-125的50%或更多以大分子形式保留。此外,凝胶色谱研究表明,注射后三小时血清中标记物质的分子大小与原始I-125-PDGF-AB相同。另外,观察到低分子量分数,表明存在降解产物。皮下给药后获得最大比例的降解材料。不存在部分降解的I-125标记片段,例如I-125寡肽表示完全降解,而不是有限的降解,表明I-125-PDGF-AB已通过细胞摄取处理。结论是,小鼠中血管外给予的PDGF-AB以完整的大分子形式吸收到血液中。该发现表明可以通过血管外施用PDGF来获得血液中完整PDGF浓度的长期增加。 [参考:25]

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