18F-FDG PET/CT显像对心肌“缺血记忆”的分子机制研究

Experimental Study of the Molecular Mechnisms of Myocardial Ischemic Memory With 18F-FDG PET/CT Imaging

  • 摘要: 建立了不同程度的犬急性心肌缺血-再灌注模型。利用18F-FDG PET/CT动态心肌显像和实时定量PCR方法探讨了缺血心肌葡萄糖代谢改变(缺血记忆)和缺血程度的关系。将8只杂种犬随机分为球囊封堵20 min组(4只)和40 min组(4只),在空腹状态下(禁食>12 h)行基础、缺血1 h和缺血24 h的18F-FDG PET/CT动态心肌显像以及99Tcm-MIBI SPECT心肌灌注显像。计算缺血区和非缺血区心肌的葡萄糖摄取率比值K。所有显像完成后处死实验犬并分别取缺血区、非缺血区心肌组织。应用实时定量PCR方法,测定葡萄糖转运体蛋白1、4(GLUT-1、GLUT-4)、心脏脂肪酸结合蛋白(H-FABP)基因的mRNA表达量。两组犬三次心肌灌注显像均未见异常。基础显像时,两组预封堵心肌与非缺血区心肌18F-FDG摄取率的比值K无明显差异;缺血1 h后,两组K值均增加,且40 min组高于20 min组;缺血24 h后,40 min组的K值仍高于基础状态,而20 min组的K值与基础状态下无明显差异。PCR结果示,两组非缺血心肌的GLUT-1、GLUT-4以及H-FABP基因mRNA表达量无明显差异,而缺血心肌的GLUT-1和GLUT-4基因mRNA表达量增加,H-FABP基因的mRNA表达量减低,且40 min组的改变较20 min组更为明显。以上结果提示,心肌缺血-再灌注后,缺血心肌对葡萄糖(18F-FDG)摄取增加的程度和持续时间(缺血记忆)与缺血的程度相关。

     

    Abstract: This study was aimed to explore whether the changes of mRNA and the existence and duration of ischemic 18F-FDG uptake correlate with the extent of myocardial ischemia in ischemia reperfusion canine model. The 20 minute (n= 4) and 40 minute (n= 4) coronary artery occlusion followed by 24 h of openartery reperfusion in canine model were performed. All dogs underwent fasting (>12 h) dynamic 18F-FDG PET/CT and 99Tcm-MIBI SPECT imaging at baseline, 1 h and 24 h after reperfusion. When all imaging were completed, myocardial samples from the ischemic and nonischemic region were obtained, and the mRNA expression of glucose transporter-1 (GLUT-1), glucose transporter-4 (GLUT-4), and heart-fatty acid binding protein (H-FABP) were estimated by Real Time PCR. There was no difference in the ratio of hypoperfused region/nomoperfused region of 18F-FDG uptake between the 20-minute group and 40 minute group at baseline. When examined at 1 h, increased 18F-FDG uptake was observed in the 40 minute group. When estimated at 24 h, only the 40 minute group showed slightly higher 18F-FDG uptake than baseline, whereas no such difference was demonstrated in the 20minute group. Similar mRNA expression of GLUT-1, GLUT-4 and H-FABP were demonstrated in the nonischemic regions between the 2 groups, whereas increased expressions of GLUT-1 and GLUT-4, and decreased H-FABP mRNA were demonstrated in the ischemic regions. The changes of mRNA expression were more obvious in the 40 minute group than in the 20-minute group.The results showed that the existence and persistent period of ischemic 18F-FDGuptake (ischemic memory) was correlated with the extent of myocardial ischemia.

     

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