STI结合MCE评价缺血后适应和药物后适应的兔心肌保护作用及其机制研究

Early diagnosis and treatment of acute myocardial infarction (AMI) are the keys for good prognosis. However, reperfusion injury will be happened after the reperfusion of AMI. Researches show that ischemia preconditioning (IPC) and ischemia postconditioning (I-PostC) can reduce some triggering factors of reperfusion injury, so as to attenuate myocardial cell damage and protect myocardial function effectively. But the clinical application is limited obviously because IPC can not be controlled and I-PostC is invasive and sometimes dangerous. Pharmaeologieal posteonditioning (P-PostC) is provided in this time, and shows very good clinical application prospect because the method is simple, noninvasive and safe. P-PostC is that, by injecting drugs through different channels just before reperfusion or within minutes of reperfusion beginning, to reduce reperfusion injury and protect myocardial function. But the research is still initial, the exact myocardial protective effect and the route, dosing and time of administration are ambiguous. This study will use ATP, oxygen free radical scavenger and calcium antagonist drugs to prepare P-PostC and I-PostC cardiac models of rabbit to evaluate the changes of left ventricular function and myocardial microcirculation perfusion by new ultrasound technology - - speckle tracking imaging ( STI ) and myocardial contrast echocardiography ( MCE ). At the same time, to explore the molecular biology mechanism of I-PostC and P-PostC through the observation and analysis of myocardial enzyme, cytokine, protein and gene expression and apoptotic cells and wish to settle a good foundation for the technology and method to clinical application.

急性心肌梗死再灌注后的再灌注损伤直接影响心肌功能恢复。缺血预适应(IPC)和缺血后适应（I-PostC）可减轻再灌注损伤的多种触发因素，保护心肌功能。然而，两者因无法预知和有创伤性使其临床应用大大受限。药物后适应（P-PostC）应运而生，即长时间缺血后，于再灌注前或开始几分钟内用药，以减轻再灌注损伤，产生保护效应。其操作简便、安全无创，临床应用前景好。但研究尚处于起步阶段，确切的心肌保护效果、给药方式、给药计量、给药时间均存在一定争议。本研究拟采用三磷酸腺苷、氧自由基清除和钙离子拮抗剂作为后适应药物，制备不同给药方式的兔心肌药物后适应及缺血后适应模型。采用超声斑点追踪成像（STI）结合心肌声学造影（MCE），评价各模型梗阻及再灌注前后的左室功能变化和心肌微循环灌注情况，比较I-PostC和不同P-PostC的心肌保护效果，探讨其分子生物学机制，以期为该技术及方法的临床应用奠定良好的基础。

冠心病（CAD）急性心肌梗死是心血管疾病死亡的首要原因，早期疏通冠状动脉堵塞、恢复缺血心肌血流是改善心脏功能的重点所在，然而急性心肌梗死再灌注后的再灌注损伤直接影响心肌功能恢复。目前，能够减轻再灌注损伤(IRI)的方法主要有缺血预适应（IPC）、缺血后适应（I-PostC）和药物后适应（P-PostC）。前两者因其不可预知性及有创性使临床应用大大受限。而P-PostC是在长时间缺血后，于再灌注前或开始几分钟内用药，以减轻IRI，产生保护效应。本研究成功制备了兔心肌缺血-再灌注、缺血后适应及药物（三磷酸腺苷和依达拉奉）后适应模型，并应用斑点追踪成像（STI）评价各模型梗阻及再灌注前后的左室功能变化和心肌微循环灌注情况。结果表明STI评价心肌保护效应准确度较高、可重复性强，与心肌酶学及病理学检测结果相吻合，验证了STI在临床评估心肌运动功能药物疗效和预后上的应用价值。同时本研究发现药物后适应对心肌缺血再灌注引起的纵向、环向、径向和扭转功能的损伤具有重要的保护作用，且该效果与缺血后适应的效果接近，能避免缺血后适应对冠状动脉造成的机械损伤。因此，药物后适应对缺血再灌注心肌保护作用具有十分重要的临床价值；本研究结果还显示，静脉及动脉给药方式的不同对心肌功能恢复无明显影响，进一步说明药物后适应具有广泛应用前景。