PHYSIOLOGICAL ACTIVITY OF PLATELET ACTIVATING FACTOR(PAF) AND ANTISHOCK ACTION OF THE PAF ANTAGONIST

血小板活化因子(PAF)在动物体内产生休克，并参与实验性内毒素休克的发病机制。它也被认为是许多病理过程中的关键介质，包括血管通透性和心功能不全。这两种物质在合成途径和生物活性上也有很强的相互作用。我们研究了特异性PAF受体拮抗剂(CV-3988、CV-6208)和LTS拮抗剂(FP-55712、ONO-1708)对内毒素诱导的全身反应和大鼠存活率的影响。内毒素休克大鼠血浆转氨酶、血小板计数和红细胞压积的变化不受CV或FPL的影响，也不能提高内毒素休克小鼠的存活率。给予长春花碱(VB)4d后，大鼠外周血白细胞数降至1200220/mm~3。给予长春花碱(VB)后，大鼠存活率显著提高，血浆转氨酶(ALT)显著降低。提示白细胞释放的PAF和LT可能在内毒素休克的发病机制中起关键作用，并与血流动力学改变和血管通透性密切相关。

Platelet activating factor (PAF) produces shock in animals and has been implicated in the pathogenesis of experimental endotoxin shock. LTs have also been suggested as key mediators in a number of pathologic processes including vasopermeability and cardiac dysfunction. These two substances have also strong interaction in their synthetic pathway and biological activities. We have studied the effect of specific PAF receptor antagonists (CV-3988,CV-6208) and LTs antagonists (FPL-55712,ONO-1708) on endotoxin-induced systemic reactions and survival rate in rats. Pretreatment with CV or FPL did not prevent the change of plasma transaminase, platelet count and hematocrit following the administration of lipopolisaccharide (LPS), and it did not improve the survival rate from endotoxin shock. On the contrary, combined pretreatments of CV and FPL or ONO improved significantly the survival rates and pre-vented the increase of hematocrit following LPS administration.Four days after the administation of vinblastine (VB), white blood cell count decreased to 1200 220/mm^3. In the rats that received VB, survival rate increased significantly and prevent the change of plasma transaminase following the adminstration of LPS. These findings suggest that PAF and LT released from the white blood cells may play a pivotal role in the pathogenesis of endotoxin shock and are closely related to the hemodynamic change and vascular permeability.