Kaku S, Umemura K, Mizuno A, Kawasaki T, Nakashima M
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Eur J Pharmacol. 1997 Mar 5;321(3):301-5. doi: 10.1016/s0014-2999(96)00971-5.
Platelet aggregation plays a important role in the thrombotic cerebral infarction. The final common mechanism in the formation of a platelet aggregate is the linking of adjacent platelets by fibrinogen binding to the platelet integrin alpha 11b beta 3. In this study, we evaluated the effect of the disintegrin, triflavin, in a rat middle cerebral artery thrombosis model. Thrombus at the left middle cerebral artery in rat was induced by photochemical reaction between rose bengal and green light, which caused endothelial injury at the site of irradiation. We measured the time to occlusive thrombus formation and the size of ischaemic cerebral damage. Triflavin dose dependently prolonged the time to occlusive thrombus formation in this model. Triflavin also reduced the size of ischaemic cerebral damage on examination at 24 h after photochemical reaction. Triflavin dose dependently inhibited ADP- and collagen-induced platelet aggregation and platelet retention in the collagen-coated beads method ex vivo. These effects were thought to result from the blockade of platelet integrin alpha IIb beta 3. Blockade of platelet integrin alpha IIb beta 3 may be useful in the prevention of cerebral arterial thrombosis.
血小板聚集在血栓性脑梗死中起重要作用。血小板聚集体形成的最终共同机制是纤维蛋白原与血小板整合素αⅡbβ3结合,从而使相邻血小板相连。在本研究中,我们在大鼠大脑中动脉血栓形成模型中评估了去整合素triflavin的作用。通过孟加拉玫瑰红与绿光之间的光化学反应诱导大鼠左侧大脑中动脉血栓形成,该反应导致照射部位的内皮损伤。我们测量了闭塞性血栓形成的时间和缺血性脑损伤的大小。在该模型中,triflavin剂量依赖性地延长了闭塞性血栓形成的时间。在光化学反应后24小时检查时,triflavin还减小了缺血性脑损伤的大小。在体外,triflavin剂量依赖性地抑制ADP和胶原诱导的血小板聚集以及胶原包被珠法中的血小板滞留。这些作用被认为是由于血小板整合素αⅡbβ3的阻断所致。阻断血小板整合素αⅡbβ3可能有助于预防脑动脉血栓形成。