Okamoto M, Yoshida K, Nishikawa M, Kohsaka M, Aoki H
Thromb Res. 1986 Jun 1;42(5):661-71. doi: 10.1016/0049-3848(86)90344-0.
PAF (1 ug/kg) injected intravenously (i.v.) into anesthetized rabbits resulted in marked loss of circulating platelets and leukocytes. Administration of FR-900452 1-methyl-3-(1-(5-methylthiomethyl-6-oxo-3-(2-oxo-3-cyclopenten-1-y lidene)- 2-piperazinyl) ethyl)-2-indolinone, a specific PAF inhibitor, at a dose of 10 mg/kg i.v. with 10 min prior to the PAF injection significantly prevented both changes. On the other hand, PAF has been considered as a mediator of endotoxin shock. Therefore, in order to determine whether endogenous PAF contributes to the occurrence of thrombocytopenia or leukopenia in endotoxin shock, we assessed the effect of FR-900452 on the thrombocytopenia and the leukopenia following bolus i.v. injection of E.coli endotoxin (0.03 mg/kg) in rabbits. As a result, pretreatment with the compound (10 mg/kg, i.v.) significantly reduced the thrombocytopenia at 60 and 180 min after the endotoxin injection. In contrast, FR-900452 did not reduced the leukopenia at any time of after endotoxin. These results indicate that PAF might be involved in the occurrence of thrombocytopenia in rabbit endotoxemia and the contribution of PAF to the leukopenia is much less extent than that to the thrombocytopenia.
将PAF（1微克/千克）静脉注射（i.v.）到麻醉的兔子体内，导致循环血小板和白细胞显著减少。在注射PAF前10分钟静脉注射10毫克/千克剂量的FR-900452（1-甲基-3-(1-(5-甲基硫代甲基-6-氧代-3-(2-氧代-3-环戊烯-1-亚基)-2-哌嗪基)乙基)-2-吲哚酮），一种特异性PAF抑制剂，可显著预防这两种变化。另一方面，PAF被认为是内毒素休克的介质。因此，为了确定内源性PAF是否导致内毒素休克中血小板减少或白细胞减少的发生，我们评估了FR-900452对兔静脉注射大肠杆菌内毒素（0.03毫克/千克）后血小板减少和白细胞减少的影响。结果，用该化合物（10毫克/千克，静脉注射）预处理可显著减轻内毒素注射后60分钟和180分钟时的血小板减少。相反，FR-900452在任何时候都没有减轻内毒素后的白细胞减少。这些结果表明，PAF可能参与兔内毒素血症中血小板减少的发生，并且PAF对白细胞减少的作用程度远小于对血小板减少的作用程度。
