超声STI多层分析技术结合负荷心肌声学造影评价兔ATP药物后适应模型及生物机制探讨

The reperfusion injury (RI) after acute myocardial infarction (AMI) directly affects the myocardial function recovery. Previous studies showed that ATP pharmacological postconditioning (ATP-PostC) can reduce some triggering factors of RI, so as to attenuate myocardial cell damage and protect myocardial function effectively. It shows very good clinical application prospect because the method is simple, noninvasive and safe. 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 to prepare P-PostC cardiac models of rabbit. The myocardial viability is determined after coronary artery obstruction and the range of ischemic myocardium is detected after reperfusion using myocardial contrast stress echocardiography (MCSE). And the subendocardial and myocardial and epicardial function of left ventricular are evaluated before and after obstruction and perfusion using the multilayer analysis technology of speckle tracking imaging (STI). Compared with MCSE and pathology, the aim was to evaluate the value of STI multilayer analysis technology to early detect myocardial dysfunction; to analyze synthetically the effect of ATP-PostC to protect myocardial function; and to explore its mechanism of molecular biology 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。前期研究表明三磷酸腺苷（ATP）药物后适应(ATP-PostC)可减轻再灌注损伤的多种触发因素，保护心肌功能，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及生物学机制有待进一步探讨。本研究拟采用ATP制备兔心肌缺血药物后适应模型，采用超声心动图新技术——斑点追踪成像(STI)多层分析技术评价模型梗阻前后、再灌注前后左室壁心内膜下、心肌、心外膜下局部心肌功能变化，采用负荷心肌声学造影(MCSE)于兔冠状动脉梗阻后判定存活心肌，再灌注前后不同时间确定心肌缺血及梗死范围，两者相互对照，并结合病理学结果评价STI 多层分析技术早期定位、定量局部心肌功能异常及MCSE判定存活心肌和梗死心肌的价值，综合分析ATP-PostC 的心肌保护效应，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。

急性心肌梗死冠脉再通后的再灌注损伤直接影响心肌功能恢复。前期我们研究了缺血后适应对家兔缺血再灌注（IR）模型的心肌保护作用，其效果较明显但临床应用受限。药物后适应(P-PostC)是近年来研究的热点，ATP是临床常用药，可减轻IR损伤的多种触发因素，保护心肌功能。本研究拟采用ATP制备兔心肌缺血药物后适应模型，采用超声斑点追踪成像(STI)分层应变评价模型梗阻前后、再灌注前后左室壁心内膜下、心肌、心外膜下局部心肌功能变化，并采用负荷超声心动图(SE)于兔冠状动脉梗阻后判定存活心肌，再灌注前后不同时间确定心肌缺血及梗死范围。结果表明，ATP-PPost组兔再灌注30min、60min及120min左室SLsys-endo, SLsys-mid, SLsys-epi 绝对值均增高（P＜0.01）；ATP-PPost组再灌注各时间点SLsys-endo, SLsys-mid, SLsys-epi绝对值较IR组均增高。多巴酚丁胺负荷后，存活节段SLsys-endo、SLsys-mid、SLsys-epi绝对值增加（P<0.05），非存活节段SLsys-endo、SLsys-mid、SLsys-epi绝对值与阻断后无明显变化，两组之间比较SLsys-endo差异有统计学意义（P<0.05）。IPostC组和ATP-PPostC组的梗死心肌百分率和凋亡细胞百分率均显著低于IR组（均P<0.05）。此外，IPostC和ATP-PPostC两组均与Bcl-2mRNA的增加和Bax mRNA的降低有关。超声STI多层分析技术检测左室心内膜、心肌和心外膜的局部心肌功能，早期反应心肌功能变化及ATP-PostC对心肌再灌注损伤的保护效应。STI结合SE能准确评估不同缺血时间心肌存活性及收缩储备变化。ATP-PPostC心肌功能的保护效应与心肌细胞凋亡的抑制有关。