【作者】 张娟娟；

【导师】 李易； 李建美； 卢竞前； 张荣华；

【作者基本信息】 昆明医学院 ， 心血管内科， 2008， 硕士

【摘要】 目的:观察急性心肌梗死(AMI)患者介入围手术期应用血小板糖蛋白(GP)Ⅱb/Ⅲa受体拮抗剂替罗非班对血清可溶性CD40配体(sCD40L)及高敏C反应蛋白(hs-CRP)水平的影响,了解GPⅡb/Ⅲa受体拮抗剂对AMI患者急性期炎症反应和斑块稳定性的抑制作用。方法:排除冠心病的对照组20例,稳定性心绞痛(SAP)患者20例,AMI患者80例(随机分为常规治疗组和替罗非班组):均为ST段抬高型急性心肌梗死(STEMI),将120例受试者分成4组:对照组(A组:20例)、稳定性心绞痛组(B组:20例)、AMI常规治疗组(C组:40例)、AMI替罗非班组(D组:40例)。C组和D组所有患者均行经皮冠状动脉介入治疗(PCI)。除A组外,B组入院后按冠心病二级预防治疗,C组和D组均接受抗血小板、抗凝治疗和/或溶栓治疗。D组于PCI术前6小时给替罗非班至术后36小时,所有受试者均于入院后即抽取静脉血5ml,而PCI术后24h再抽取C组和D组患者静脉血5ml,测定血清sCD40L及hs-CRP,比较组间及组内sCD40L及hs-CRP水平在PCI术前术后及用药前后的差异,探讨GPⅡb/Ⅲa受体拮抗剂替罗非班对AMI患者炎症反应和动脉粥样斑块稳定性的影响。C组和D组PCI术后随访1月,观察1月内主要不良心脏事件(MACE)以及出血情况。结果:1.C组和D组两组患者术前血清sCD40L及hs-CRP水平均显著高于B组和A组(p＜0.01),B组患者血清sCD40L水平高于A组,但无统计学意义(p＞0.05),而B组患者hs-CRP较A组为高,有显著性差别(p＜0.05)。2.PCI术前C组和D组sCD40L及hs-CRP水平无明显差异(p＞0.05),但C组和D组两组患者术后血清sCD40L及hs-CRP水平明显高于术前(p＜0.01),且PCI术后D组sCD40L及hs-CRP水平较C组明显降低(p＜0.01)。3.直线相关性分析表明:AMI患者血清sCD40L及hs-CRP水平显著相关(r=0.894,p＜0.05)。4.C组和D组两组在PCI术后1月内MACE发生率,D组低于C组,有统计学差异(p＜0.05)。5.C组和D组两组患者在治疗及随访期间均未见严重出血,但D组患者有6例(15%)出现轻度血小板减少和出血,较C组(2.5%)明显增多(p＜0.05)。结论:1.AMI的发生发展过程存在炎症反应,对照组、SAP患者、AMI患者sCD40L和hs-CRP水平逐级升高,提示它们可能是冠脉病变的活动性标志,高水平的sCD40L可能代表着斑块的不稳定状态。血清sCD40L和hs-CRP水平有一定的相关性,可作为炎症标志物对于AMI的发生发展有一定的预测价值。2.PCI术后血清sCD40L及hs-CRP水平明显高于术前,可能与术后局部炎症反应增强或局部内膜撕裂有关,所以PCI术后应加强抗炎治疗。3.GPⅡb/Ⅲa受体拮抗剂替罗非班在介入围手术期应用可以改善AMI患者梗死相关血管TIMI血流、减少MACE的发生。4.GPⅡb/Ⅲa受体拮抗剂替罗非班可明显降低血清sCD40L及hs-CRP水平,对AMI患者的治疗不仅抑制血小板聚集,可能还有助于动脉粥样斑块的稳定,具有独立于抗血小板之外的非特异性的抗炎作用。为围介入手术期使用GPⅡb/Ⅲa受体拮抗剂治疗AMI提供理论依据。更多还原

【Abstract】 Objective: To study the effects of platelet glycoprotein(GP) IIb/IIIa receptor antagonist tirofiban on blood serum soluble CD40 ligand(sCD40L) and high sensitivety C react protein(hs-CRP) perioperative intervention in acute myocardial infarction (AMI), and to investigate the role of inflammation on AMI and the influence of GP IIb/IIIa receptor antagonist on the inflammatory reaction and the stability of plaque. It also probed the significance of changes in sCD40L through the research of the relevance of sCD40L and hs-CRP.Methods: Selecting 20 non-coronary heart disease adults for control group, 20 stability angina pectoris(SAP) patients, 80 AMI patients divided into conventional therapy group and tirofiban group stochastically, and treating 120 subjects with A, B, C, D groups respectively: control group(group A: n=20), SAP group(group B: n=20), conventional therapy group: treated without tirofiban (group C: n=40), tirofiban group: treated with tirofiban(group D: n=40).Both group C and group D underwent percutaneous coronary intervention (PCI) . Except for group A, group B received secondary prevention of coronary heart disease treatment, group C and group D accepted antiplatelet, anticoagulant therapy and or thrombolysis therapy. Group D: tirofiban was initiated 6 hours before PCI according to the standard dose (tirofiban was administered intravenously with a loading dose of 10μg/kg for 3 minutes, followed by infusion of 0. 15μg/(kg. min). Maintained infusion was given for 36 hours after PCI) . All SAP and AMI patients who were selected were collected venous blood 5ml as soon as possible. AMI patients were collected blood sample again 24 hours after PCI. We measured the density of serum sCD40L and hs-CRP, then compared the difference of sCD40L and hs-CRP among different groups. To investigate the relationship of inflammationgs and AMI, explore the influcence of GPIIb/IIIa receptor antagonist tirofiban on the inflammatory reaction and the stability of artery atheromatous plaque. Both group C and group D was following up 30 days after PCI, and observed the major adverse cardiac events(MACE) during 30 days.Results: 1.The level of the serum sCD40L and hs-CRP in AMI patients was significantly higher than that in group B and group A (p < 0. 01). The serum sCD40L in group B was higher than that in group A, but there was no difference between group B and group A of sCD40L (p>0. 05), and there was obvious difference of the density of the serum hs-CRP between group B and group A (p < 0.05). 2. Comparisons of sCD40L and hs-CRP between C and D group before operation: there was no difference between group C and group D of the two markers (p > 0. 05), however, not only in group C but also in group D the level of sCD40L and hs-CRP 24 hours after PCI was obviously higher than that preoperation (p<0. 01), and the level of sCD40L and hs-CRP degrade obviously 24 hours after operation in group D (p < 0.01). 3. The straight linear relevance analysis showed that the sCD40L and hs-CRP were relevant. The relevance of sCD40L and hs-CRP r=0.894(p < 0. 05). 4. During the follow-up of 30 days after PCI, MACE were significantly less frequent in group D than group C(p< 0. 05). 5. No serious hemorrhage was observed in both group C and group D during in-hospital, however, more patients with minor hemorrhage and thrombocytopenia in group D(15% vs 2.5%, p<0. 05).Conclusion: 1. Inflammation reaction exists in the development of AMI. The elevated sCD40L and hs-CRP may be the activating signs of coronary artery disease. The high level of sCD40L may represent instability of the plaque.The serum sCD40L and hs-CRP have some relevance. sCD40L can be used as markers of inflammation as serum hs-CRP. They have some predictive value for the development of AMI. 2. The level of sCD40L and hs-CRP 24 hours after PCI was obviously higher than that preoperation. This may be concerned with the enhanced local inflammatory reaction or partial tear of the intima after PCI. Therefore, it is necessary that strengthens anti-inflammatory treatment after PCI. 3. GPII b/IIIa receptor antagonist can improve the infarct-related artery TIMI flow of AMI patients, reduce the occurrence of MACE. 4. GPIIb/IIIa receptor antagonist tirofiban can degrade the levels of serum sCD40L and hs-CRP. Tirofiban not only inhibits platelet aggregation, but also may contribute to the stability of atherosclerotic plaque, nonspecific anti-inflammatory action is independent of the anti-platelet effect. They provide theoretical basis for identifying the unstable plaque in clinical and applying GP IIb/IIIa receptor antagonist preoperative intervention for AMI.更多还原