5-HT_（2A）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
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-HT_(2A)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-HT_(2A)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-HT_(2A)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
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-HT_(2A) 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-HT_(2A) 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
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-HT_(2A) 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-HT_(2A) 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
引文
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