Sinzinger H, Neumann I, O'Grady J, Rogatti W, Peskar B A
Wilhelm Auerswald-Atherosclerosis Research Group (ASF), Vienna, Austria.
Prostaglandins Leukot Essent Fatty Acids. 1997 Apr;56(4):325-30. doi: 10.1016/s0952-3278(97)90577-9.
Prostaglandin (PG) E1 has been shown to improve thromboresistance. This experiment was designed to examine whether an effect on the arterial wall or the platelets is responsible for this phenomenon. Using a cross-perfusion model, the aortic and iliac artery endothelium of rabbits was removed by a balloon catheter before being perfused with blood of donor rabbits. Donor and/or receiver animals were treated with 20 microg PGE1 or vehicle (cyclodextrin) intravenously daily for 1 week. After the last administration of PGE1 or its vehicle, the animals were killed and native blood from a donor rabbit was recirculated (30 ml/min) via a deendothelialized segment of a receiver rabbit. The contact (C) and spread (S) platelets as well as the denuded surface covered with platelet aggregates (> 5 microm in height) were quantified by morphometry. Deposition of (111)In-oxine labeled autologous platelets was quantitatively determined per surface unit. In addition, PGI(2)- and TXB2-formation by the denuded aortic and iliac artery segments was determined. Pretreatment of receiver rabbits with PGE1 resulted in morphometrically assessed decreased platelet adhesion and aggregation, even when the donor rabbit was vehicle-treated. A vehicle-treated receiver rabbit, in contrast, shows platelet deposition comparable to controls, even if the donor rabbit was PGE1-pretreated. Treatment of donor animals with PGE1 did not result in a reduction in thrombogenicity. The beneficial in vivo PGE1 action of decreased arterial thrombogenicity is thus mediated by an effect on the vascular wall rather than on circulating platelets.
前列腺素(PG)E1已被证明可改善抗血栓形成能力。本实验旨在研究这种现象是由对动脉壁还是血小板的作用引起的。采用交叉灌注模型,在向兔主动脉和髂动脉灌注供体兔血液之前,用球囊导管去除其内皮。供体和/或受体动物每天静脉注射20微克PGE1或赋形剂(环糊精),持续1周。在最后一次给予PGE1或其赋形剂后,处死动物,将供体兔的全血通过受体兔的去内皮段再循环(30毫升/分钟)。通过形态计量学对接触(C)血小板和铺展(S)血小板以及覆盖有血小板聚集体(高度>5微米)的裸露表面进行定量。定量测定每单位表面(111)铟-奥克辛标记的自体血小板沉积量。此外,还测定了去内皮的主动脉和髂动脉段生成PGI(2)和TXB2的情况。即使供体兔接受赋形剂处理,用PGE1预处理受体兔也会在形态计量学上显示血小板粘附和聚集减少。相反,即使供体兔接受PGE1预处理,接受赋形剂处理的受体兔的血小板沉积与对照组相当。用PGE1处理供体动物并没有导致血栓形成性降低。因此,PGE1在体内降低动脉血栓形成性的有益作用是通过对血管壁而非循环血小板的作用介导的。