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5-HT2A受体在心肌缺血、缺血/再灌注时血小板及血管高反应性中的作用

The Role of 5-HT2A Receptor in Hyperreactivity of Platelet and Artery during Myocardial Ischemia、Myocardial Ischemia/reperfusion

【作者】 庞懿

【导师】 薛全福; 许澍淮;

【作者基本信息】 中国协和医科大学 , 病理生理学, 1998, 博士

【摘要】 在动脉粥样硬化时,血小板和血管间的相互作用在冠心病事件中起重要作用。血小板激活后释放多种血管活性物质,促进血栓形成,并引起血管收缩反应。其中,血小板释放的5-HT在血小板聚集和血管痉挛中发挥重要作用。当血小板在受损的血管表面粘附、聚集和激活后,可释放大量的5-HT,后者通过刺激血小板表面的5-HT2A受体,使血小板进一步激活,从而形成恶性循环,诱发血栓形成,5-HT2A受体拮抗剂有明显抑制血栓形成的作用。生理状态下5-HT是血小板弱的激活剂。它引起的血小板聚集是可逆的,因此冠心病时5-HT引起的血小板聚集并发展成血栓与此时血小板对5-HT的反应性增高有关。本室以前的部分工作表明冠心病患者存在血小板对5-HT的高反应,蛇毒抗栓酶(SVATE)可抑制这种高反应性,并设想血小板对5-HT的高反应性可能与血小板上5-HT2A受体的变化有关,但到目前为止,尚未见这方面的报道。5-HT在冠心病中另一重要作用是它能诱发冠脉痉挛。向冠心病患者冠脉内注入不引起正常人冠脉收缩的低剂量的5-HT可诱发典型的冠脉痉挛和心肌缺血。在粥样硬化的离体动脉(主动脉,颈动脉,冠状动脉)上,5-HT引起的血管收缩反应要比正常动脉的收缩反应强得多。这种动脉血管对5-HT的高反应性与动脉粥样硬化有密切的关系,而且显然是由于动脉血管本身

【Abstract】 Interaction between platelets and arterial wall induced by pathogenetic factors plays an important role in the pathogenesis of coronary heart disease(CHD). A lot of vasoactive agents released from aggregated platelet contribute to thrombosis and vascular contraction, which will lead to myocardial ischemia and infarction. Studies implicated that 5-HT, when released from aggregated platelets, is extremly important in inducing platelet aggregation and coronary artery spasm. Platelet aggregated at any site of injuried artery wall, will release more 5-HT, which further in turn stimulate 5-HT2A receptor located in platelet membrane. As a result, more platelet aggregates and a vicious cycle is formed. In physiological state, 5-HT is just a weak inducer of platelet aggregation, and this aggregation is reversible. However, the circumstance is quite different in CHD, in which platelet become more sensitive to 5-HT compared with normal. Our previous studies showed that platelet aggregation induced by 5-HT in patients with acute mycardial infarction was significantly higher than that of control, and snake venom anti-thrombosis enzyme(SVATE) could inhibit the platelet hyperreactivity incuced by 5-HT. No data were shown whether platelet 5-HT2A receptor changed and contributed to platelet hyperreactivity in those patients. Another important role of 5-HT in CHD is that 5-HT can induce coronary arterial spasm. In patients with angina, intracoronary infusion of 5-HT with concentration only leads to normal coronary arterial dilation could induce

  • 【分类号】R363
  • 【下载频次】135
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