^13N—NH3 PET及冠状动脉造影评价CD151基因转染对小型猪心肌梗死后血流灌注的影响

The study with ^13N-NH3 PET and coronary angiography to investigate the effect of CD151 gene therapy on swines with experimental myocardial infarction

目的用^13N—NH，PET及冠状动脉造影共同评价CD151基因转染促小型猪心肌梗死后血运重建。方法结扎20头小型猪冠状动脉左前降支（LAD），建立心肌梗死模型。对梗死区及梗死周围心肌直接注射CD151及绿色荧光蛋白（GFP）重组腺相关病毒（rAAV）进行基因转染。8周后用免疫组织化学方法分析心肌组织CD151蛋白的表达和心肌组织微血管密度，用^13N—NH，PET显像评价心肌血流灌注，用LAD造影评价侧枝循环的建立。采用SPSS11．0软件行配对t检验或方差分析（ANOVA）。结果CD151基因转染促进局部心肌组织CD151高表达并增加缺血区心肌组织微血管密度。rAAV—CD151组心肌血流灌注明显增加，心肌缺血总分值为10．82±2．36，明显小于rAAV—GFP组（19．33±1．67，t=5．86，P=0．002）。冠状动脉造影显示rAAV—CD151组缺血心肌的侧枝循环建立明显较rAAV—GFP组增加。结论CD151基因转染可以明显促进心肌梗死后血运重建、增加血流灌注。^13N—NH，PET及冠状动脉造影能直观地评价心肌血运重建。

Objective Our previous studies showed that CD151 could promote neovascularization in a rat hind-limb ischemia model and in a rat myocardial ischemia model. This study was to determine the change of myocardial perfusion and coronary collateralization after intramyocardial administration CD151 in swines with experimental myocardial infarction. Methods CD151 and antiCD151 were constructed into the recombinant adeno-associated virus vector （rAAV）. Twenty swines received coronary artery ligation and in- tramuscular injection of rAAV-CD151 or rAAV-green fluorescent protein （GFP）. Eight weeks after vector administration, the expression of CD151 protein and the capillary density were measured using immunohisto-chemistry. Regional myocardial perfusion was evaluated by ^13N-NH3 PET. Coronary angiography was performed to assess collateral vessels reconstruction. The t-test or ANOVA with SPSS 11.0 was used for data analysis. Results High levels of CD151 protein expression and capillary density were detected in the rAAV- CD151 group. ^13N-NH3 PET imaging showed that myocardial pcrfusion was improved and the myocardial ischemia scores were significantly decreased in the rAAV-CD151 group when compared with rAAV-GFP group （ 10.82 ± 2.36 vs 19.33 ±1.67, t = 5.86, P = 0.002 ）. Coronary angiography confirmed better collateral circulation in the rAAV-CD151 group. Conclusions rAAV-CD151 direct injection can transfect the myocardium and express the CD151 protein, thereby significantly improve the myocardial blood perfusion and coronary collateralization. ^13 N-NH3 PET and coronary angiography can be used directly to evaluate the collateral vessel reconstruction and perfusion status of swine myocardium.