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

血小板活化因子(PAF)的生理活性及PAF拮抗剂的抗休克作用

基本信息

批准号：
62570699
负责人：
GOTO Fumio
金额：
$ 1.15万
依托单位：
GUNMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

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.

血小板活化因子（PAF）在动物中产生休克，并与实验性内毒素休克的发病机制有关。lt也被认为是许多病理过程的关键介质，包括血管渗透性和心功能障碍。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（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预处理不能预防内毒素休克后血浆转氨酶、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。相反，CV和FPL或ONO联合预处理显著提高了存活率，并阻止了LPS给药后红细胞压积的增加。给予长春花碱（VB） 4 d后，白细胞计数降至1200 220/mm^3。注射VB的大鼠存活率明显提高，且LPS对血浆转氨酶无明显影响。这些结果提示，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。