血小板激活因子对大鼠肺血管通透性的影响：血小板和多形核白细胞的作用。

Effect of PAF on rat lung vascular permeability: role of platelets and polymorphonuclear leucocytes.

作者信息

Sirois M G, de Lima W T, de Brum Fernandes A J, Johnson R J, Plante G E, Sirois P

机构信息

Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, P.Q., Canada.

出版信息

Br J Pharmacol. 1994 Apr;111(4):1111-6. doi: 10.1111/j.1476-5381.1994.tb14859.x.

DOI:10.1111/j.1476-5381.1994.tb14859.x

PMID:8032597

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1910145/

Abstract

The objectives of the present experiments were to assess the contribution of polymorphonuclear leucocytes (PMNLs), platelets and their products such as thromboxane A2 (TxA2), histamine and 5-hydroxytryptamine to platelet activating factor (PAF)-mediated protein extravasation in rat lungs. 2. Intravenous injection of PAF (1.0 and 5.0 micrograms kg-1) increased dose-dependently (up to 7.5 fold) the vascular permeability of the trachea, upper and lower bronchi to Evans blue dye (EB), a marker of albumin extravasation. The permeability of the pulmonary parenchyma was not affected significantly by PAF. 3. Thrombocytopenia induced by administration of the IgG fraction of goat anti-rat platelet serum (APS; 15 mg 100 g-1, i.p., 16-18 h) reduced by 55, 58 and 40% the effects of the lower dose of PAF (1.0 microgram kg-1) and by 31, 23 and 15% the effects of the higher dose of PAF (5.0 micrograms kg-1) on the permeability of the trachea, upper and lower bronchi respectively to albumin. 4. PMNL depletion induced by administration of rabbit anti-rat polymorphonuclear serum (ANS; 2 mg kg-1, i.v., 24 h) did not reduce significantly the effects of the lower dose of PAF (1.0 microgram kg-1) on the airways, however the effects of the higher dose of PAF (5.0 micrograms kg-1) on the permeability of the trachea, upper and lower bronchi to albumin were reduced by 43, 25 and 23% respectively. 5. The injection of both the anti-platelet and the anti-PMNL sera reduced by 61, 62 and 96% the effects of the lower dose of PAF (1.0 microg kg-1) and by 44, 39 and 47% the effects of the higher dose of PAF (5.0 microg kg-1) on the permeability of the trachea, upper and lower bronchi respectively.6. The combined injection of the TxA2-mimetic (U-44069; 5.0 microg kg-1) and PAF (1.0 and 5.0 microg kg-1)in thrombocytopenic rats overcame the vascular permeability decrease induced by APS treatment.7. Pretreatment of the animals with a combination of antagonists to histamine (mepyramine;3.0 mg kg-1) and 5-hydroxytryptamine (methysergide; 2.5 mg kg-1) did not cause a significant inhibition of the effect of PAF (1.0 and 5.0 microg kg-1) on EB extravasation in the airways.8. These data show that the effect of intravenous PAF on rat vascular permeability is partly modulated by polymorphonuclear leucocyte and platelet activation. Our results suggest that following its release,TxA2 could increase postcapillary hydrostatic pressure by inducing a venoconstriction and potentiate the extravasation elicited by PAF. These results do not suggest a major role for histamine and/or 5-hydroxytryptamine on PAF-induced albumin extravasation.

摘要

本实验的目的是评估多形核白细胞（PMNLs）、血小板及其产物如血栓素A2（TxA2）、组胺和5-羟色胺对血小板活化因子（PAF）介导的大鼠肺蛋白外渗的作用。2. 静脉注射PAF（1.0和5.0微克/千克）剂量依赖性地（高达7.5倍）增加气管、上下支气管对伊文思蓝染料（EB）的血管通透性，EB是白蛋白外渗的标志物。肺实质的通透性未受到PAF的显著影响。3. 腹腔注射山羊抗大鼠血小板血清（APS；15毫克/100克，16 - 18小时）诱导的血小板减少，使低剂量PAF（1.0微克/千克）对气管、上下支气管白蛋白通透性的影响分别降低了55%、58%和40%，使高剂量PAF（5.0微克/千克）的影响分别降低了31%、23%和15%。4. 静脉注射兔抗大鼠多形核血清（ANS；2毫克/千克，24小时）诱导的PMNL耗竭，未显著降低低剂量PAF（1.0微克/千克）对气道的影响，然而高剂量PAF（5.0微克/千克）对气管、上下支气管白蛋白通透性的影响分别降低了43%、25%和23%。5. 注射抗血小板和抗PMNL血清，使低剂量PAF（1.0微克/千克）对气管、上下支气管通透性的影响分别降低了61%、62%和96%，使高剂量PAF（5.0微克/千克）的影响分别降低了44%、39%和47%。6. 在血小板减少的大鼠中联合注射TxA2模拟物（U - 44069；5.0微克/千克）和PAF（1.0和5.0微克/千克）克服了APS治疗引起的血管通透性降低。7. 用组胺拮抗剂（美吡拉敏；3.0毫克/千克）和5-羟色胺拮抗剂（甲基麦角新碱；2.5毫克/千克）联合预处理动物，未对PAF（1.0和5.0微克/千克）对气道EB外渗的作用产生显著抑制。8. 这些数据表明，静脉注射PAF对大鼠血管通透性的作用部分受多形核白细胞和血小板活化的调节。我们的结果表明，TxA2释放后可通过诱导静脉收缩增加毛细血管后流体静压，并增强PAF引起的外渗。这些结果未表明组胺和/或5-羟色胺在PAF诱导的白蛋白外渗中起主要作用。