Yamashita M
Department of Emergency Medicine, University of Tsukuba, Japan.
Thromb Res. 1997 Aug 1;87(3):323-9. doi: 10.1016/s0049-3848(97)00134-5.
We recently showed that both plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) are induced after a massive hemorrhage. In this study, we determined if bactericidal/permeability-increasing protein (BPI) has any effects on the induction of these factors after hemorrhagic shock. Three days after cannulation, rats were bled and maintained at a mean blood pressure of 40 mmHg for 60 min, and then were resuscitated with the shed blood and an equal volume of saline over 60 min. Rats in the BPI group were given at 6 mg/kg of rBPI21 (XOMA, Berkeley, CA; a 3-mg/kg dose at the beginning of hemorrhage followed by two doses of 1.5 mg/kg at the end of shock and at the end of resuscitation). The control group was treated similarly to the BPI group, but received control protein in the same dose as rBPI21. Plasma endotoxin concentration, whole blood clotting time (WBCT) and plasma PAI activity were measured at times 0, 2, 4, 6, and 8 h. The time-course changes in mRNA of TF, PAI-1, tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) were also detected in the liver by reverse transcription and polymerase chain reaction. The plasma endotoxin levels increased after hemorrhagic shock and showed a peak at 2 h in the control group. These increases were significantly neutralized by rBPI21 treatment at 2 h in the BPI group. WBCT decreased and PAI activity increased rapidly after hemorrhagic shock in the control group. These changes were significantly smaller in the BPI group at 6 and 8 h. The increases in mRNA of TF, PAI-1, TNF alpha, and IL-6 were also attenuated by rBPI21 treatment. These results show that BPI ameliorates hypercoagulability after hemorrhagic shock and suggest that endotoxin plays a role in the pathogenesis of thrombogenic responses after hemorrhagic shock.
我们最近发现，大量出血后纤溶酶原激活物抑制剂-1（PAI-1）和组织因子（TF）均会被诱导产生。在本研究中，我们确定杀菌/通透性增加蛋白（BPI）对失血性休克后这些因子的诱导是否有任何影响。插管3天后，对大鼠进行放血，并使其平均血压维持在40 mmHg达60分钟，然后在60分钟内用放出的血液和等量的生理盐水进行复苏。BPI组大鼠给予6 mg/kg的重组BPI21（XOMA公司，伯克利，加利福尼亚州；出血开始时给予3 mg/kg剂量，休克结束时和复苏结束时各给予1.5 mg/kg剂量）。对照组的处理方式与BPI组相似，但给予与重组BPI21相同剂量的对照蛋白。在0、2、4、6和8小时测量血浆内毒素浓度、全血凝血时间（WBCT）和血浆PAI活性。还通过逆转录和聚合酶链反应检测肝脏中TF、PAI-1、肿瘤坏死因子α（TNFα）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的mRNA随时间的变化。失血性休克后对照组血浆内毒素水平升高，并在2小时达到峰值。BPI组在2小时用重组BPI21处理可显著中和这些升高。对照组失血性休克后WBCT降低，PAI活性迅速升高。BPI组在6和8小时这些变化明显较小。重组BPI21处理也减弱了TF、PAI-1、TNFα和IL-6的mRNA升高。这些结果表明，BPI可改善失血性休克后的高凝状态，并提示内毒素在失血性休克后血栓形成反应的发病机制中起作用。
