Aïssa J, Nathan N, Arnoux B, Benveniste J
INSERM U 200, Clamart, France.
Eur J Pharmacol. 1996 Apr 29;302(1-3):123-8. doi: 10.1016/0014-2999(96)00069-6.
The origin of the thrombocytopenia and leucopenia induced by protamine-heparin complexes is unknown. We studied the biochemical and cellular effects of protamine (6 mg x kg-1, i.v.) injected after heparin (5 mg x kg-1, i.v.) in New Zealand rabbits. After protamine injection (0.5 min) increases in blood platelet-activating factor (PAF-acether, PAF) (27.6 +/- 27.6 to 148.2 +/- 48.9 pg x ml-1, P < 0.05), thrombocytopenia (403 +/- 64 to 166 +/- 13 cells x 10(-3) x mm-3, P < 0.05) and leucopenia (7650 +/- 930 to 4300 +/- 668 cells x mm-3, P < 0.05) were noted. Plasma thromboxane B2 increased at 1 min (125.6 +/- 24.4 to 879.7 +/- 141.0 pg x ml-1, P < 0.01). Protamine alone induced no change. Indomethacin (3 mg x kg-1, i.v.) did not counteract the effects of heparin-protamine. Pretreatment with the PAF receptor antagonist BN 52021 [9H1, 7a-(epoxymethano)-1 H,6aH-cyclopenta[c]furo[2,3-b]furo-[3',2',3,4]cyclopenta[1,2-d]fur an-5,9, 12(4H)trione,3-tert-butylhexahydro-4,7b,11 hydroxy-8 methyl] alone (3 mg x kg-1, i.v.) delayed thrombocytopenia and reduced plasma thromboxane B2 concentration but did not modify leucopenia. Thus thrombocytopenia and thromboxane B2 release triggered by heparin-protamine may be potentiated by the release of PAF.
鱼精蛋白 - 肝素复合物所致血小板减少和白细胞减少的病因尚不清楚。我们研究了在新西兰兔静脉注射肝素（5mg/kg）后静脉注射鱼精蛋白（6mg/kg）的生化和细胞效应。注射鱼精蛋白后（0.5分钟），血小板活化因子（PAF - 乙酰醚，PAF）升高（从27.6±27.6至148.2±48.9pg/ml，P<0.05），出现血小板减少（从403±64至166±13个细胞×10⁻³/mm³，P<0.05）和白细胞减少（从7650±930至4300±668个细胞/mm³，P<0.05）。血浆血栓素B2在1分钟时升高（从125.6±24.4至879.7±141.0pg/ml，P<0.01）。单独注射鱼精蛋白未引起变化。吲哚美辛（3mg/kg，静脉注射）不能抵消肝素 - 鱼精蛋白的作用。用PAF受体拮抗剂BN 52021[9H1,7a - （环氧亚甲基）-1H,6aH - 环戊[c]呋喃[2,3 - b]呋喃[3',2',3,4]环戊[1,2 - d]呋喃 - 5,9,12（4H）三酮，3 - 叔丁基六氢 - 4,7b,11 - 羟基 - 8 - 甲基]单独预处理（3mg/kg，静脉注射）可延迟血小板减少并降低血浆血栓素B2浓度，但不能改变白细胞减少。因此，肝素 - 鱼精蛋白引发的血小板减少和血栓素B2释放可能因PAF的释放而增强。
