Takeda Y
J Clin Invest. 1972 Jun;51(6):1363-77. doi: 10.1172/JCI106932.
In vivo plasminogen responses to various stimuli were studied. Plasminogen-(125)I was prepared and used first for metabolic studies of plasminogen in control dogs. The average results were: the plasma plasminogen, 29.3+/-4.1 (SD) mg/kg; the interstitial plasminogen, 8.79+/-4.47 (SD) mg/kg; the half-life of plasma plasminogen-(125)I, 2.81+/-0.24 (SD) days; the fractional direct catabolic rate of plasminogen (j(3)), 0.295 day(-1); and the catabolic (synthetic) rate of plasminogen, 8.61+/-1.35 (SD) mg/kg per day. Studies were then made of the plasminogen-(125)I responses in dogs to a single injection of urokinase (A) and typhoid vaccine (B), and to vascular injury (C), which was produced by the damage of venous endothelium by a phenol injection. Effects of heparin were also studied in dogs given the phenol injection (D). Disc electrophoretic analysis of plasma showed generation of plasmin-(125)I in all except the control experiments. The duration of plasmin-(125)I generation was about 6 hr in A, 6 hr in B, and at least 5 days in C. Heparinization (D) shortened the duration of generation to about 6 hr. For further quantitative analysis of the tracer data, a model for coexistent plasminogen-(125)I and plasmin-(125)I was proposed and validated, from which some new analytical methods were derived. Using these methods, the average fractional rate of plasmin-(125)I generation from plasminogen-(125)I (j(4)) was 0.41 day(-1) in A, 0.30 day(-1) in B, 0.324 day(-1) in C, and 0.382 day(-1) in D. Further mathematical consideration showed that j(3) was zero at least in C during plasmin generation. Plasminogen synthesis was unchanged in all experiments. The average fractional breakdown rate of plasmin-(125)I (j(5)) in A, B, C, and D was 1.19, 1.13, 1.35, and 1.11 day(-1), respectively, and were closely similar. These results indicate that under normal conditions a major portion of plasminogen is directly catabolized without the formation of plasmin, but that significant amounts of plasmin were generated under the conditions described, that the normal process of direct breakdown of plasminogen is abolished during plasmin generation at least in C, and that the potential value of j(5) determination should be further explored.
研究了体内纤溶酶原对各种刺激的反应。制备了纤溶酶原 -（125）I，并首先用于对照犬体内纤溶酶原的代谢研究。平均结果如下：血浆纤溶酶原，29.3±4.1（标准差）mg/kg；组织间隙纤溶酶原，8.79±4.47（标准差）mg/kg；血浆纤溶酶原 -（125）I的半衰期，2.81±0.24（标准差）天；纤溶酶原的直接分解代谢分数率（j(3)），0.295天-1；纤溶酶原的分解代谢（合成）率，8.61±1.35（标准差）mg/kg per day。随后研究了犬体内纤溶酶原 -（125）I对单次注射尿激酶（A）和伤寒疫苗（B）以及血管损伤（C）的反应，血管损伤是通过苯酚注射损伤静脉内皮产生的。还研究了在接受苯酚注射的犬（D）中肝素的作用。血浆的圆盘电泳分析显示，除对照实验外，所有实验中均产生了纤溶酶 -（125）I。纤溶酶 -（125）I的产生持续时间在A中约为6小时，在B中为6小时，在C中至少为5天。肝素化（D）将产生持续时间缩短至约6小时。为了对示踪数据进行进一步的定量分析，提出并验证了一个纤溶酶原 -（125）I和纤溶酶 -（125）I共存的模型，并从中推导了一些新的分析方法。使用这些方法，纤溶酶原 -（125）I产生纤溶酶 -（125）I的平均分数率（j(4)）在A中为0.41天-1，在B中为0.30天-1，在C中为0.324天-1，在D中为0.382天-1。进一步的数学分析表明，至少在纤溶酶产生期间的C中j(3)为零。在所有实验中纤溶酶原合成均未改变。A、B、C和D中纤溶酶 -（125）I的平均分解分数率（j(5)）分别为1.19、1.13、1.35和1.11天-1，且非常相似。这些结果表明，在正常情况下，大部分纤溶酶原直接被分解代谢而不形成纤溶酶，但在所述条件下产生了大量纤溶酶，至少在C中纤溶酶产生期间纤溶酶原的直接分解正常过程被消除，并且j(5)测定的潜在价值应进一步探索。
