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

血小板活化因子（PAF）可引起动物休克，并参与实验性内毒素休克的发病机制。LT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障碍。这两种物质在合成途径和生物活性方面也有很强的相互作用。本文研究了PAF受体特异性拮抗剂CV-3988、CV-6208和LTs拮抗剂FPL-55712、ONO-1708对内毒素诱导的大鼠全身反应和存活率的影响。CV或FPL预处理不能阻止脂多糖（LPS）引起的血浆转氨酶、血小板计数和红细胞压积的变化，也不能提高内毒素休克的存活率。而CV、FPL或ONO联合预处理可显著提高存活率，并抑制LPS引起的红细胞压积升高，长春碱（VB）处理4天后，白色细胞计数降至1200 ~ 220/mm^3。VB组大鼠存活率明显提高，并能防止LPS引起的血浆转氨酶变化。提示白色血细胞释放的PAF和LT可能在内毒素休克的发病机制中起重要作用，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.