Study on the mechanical analysis of septic shock and its theraputic strategy

对休克机制的分析。我们重新评估了在感染性休克中起主要作用的肿瘤坏死因子/Cachectin。我们重新研究了重组肿瘤坏死因子(Dai Nippon Phamaco.)的休克作用。这种方法已经被Cerami在同一模型中重新使用。这种肿瘤坏死因子不会引起大鼠的休克状态。这种肿瘤坏死因子的内毒素含量(20pg-内毒素/g-肿瘤坏死因子)比Cerami所用的肿瘤坏死因子(0.4mU/mg-肿瘤坏死因子)低得多。但我们的肿瘤坏死因子加内毒素注射可能会使大鼠进入休克状态。根据这一结果，少量的内毒素和肿瘤坏死因子的作用比单独作用更强。Simillary，我们重新研究了白毒素(由小泽报道)，它是一种休克诱导剂。将合成的白蛋白注射到大鼠体内。他们死于严重的肺出血，没有低血压。他们的死亡被认为是由Shwartzman反应引起的。这些结果表明，肿瘤坏死因子或白斑毒素不是导致感染性休克的主要物质。我们现在正在对IL-1进行进一步的研究。PMX-F或蛋白水解酶抑制剂乌司他丁治疗犬感染性休克我们对大肠杆菌诱导的感染性休克进行了PMX-F治疗。PMX-F治疗可延长小鼠的存活时间(对照组；18小时；治疗组；3~7天)。PMX-F治疗组各项指标(主要是细菌计数、血糖水平)均有改善。我们用乌司他丁代替PMX-F进行了同样的实验。通过该治疗，可延长犬的存活时间，改善心输出量、低血压、心功能本身。

Analysis of shock mecanism. We re-evaluate the TNF/Cachectin which plays a main role in septic shock. We re-examine the shock-action of recombinant TNF (Dai Nippon Phamaco.). This method has been re-employed in the same model by Cerami. This kind of TNF does not induce the shock state in the rat. This TNF containd much less endotoxin ( 20 pg-LPS/g-TNF ) than TNF (0.4mu/mg-TNF) used by Cerami. But our TNF plus LPS administration could lead the rat into the shock state. According to this results, small amount of LPS and TNF act more stronger than each one. Simillary we re-studied leukotoxin (reported by Ozawa) which is one of the shock-inducing madiator. Synthetic leucotoxin was injected into rat. They died in a result of severe lung hemorrhage without hypotension. Their death is concidered to be caused by shwartzman reaction. These results indicate that TNF or Leukotoxin does not play a main substance leading to septic shock. We are now performing further study on IL-1. Treatment of septic shock in the dog by PMX-F or protease inhibitor (Urinastatin). We performed the PMX-F treatment for the E. coli-induced septic shock. PMX-F treatment prolonged the survival time (Control group; 18 hr<,Treated group; 3-7 days>). Various parameters (mainly bacterial counts, serum-glucose level) improving in the PMX-F treatment group. We performed the same above mentioned experiment by using urinastatin instead of PMX-F. By this treatment, canine was prolonged survival time and improved cardiac output, hypotension, RES-function itself.