小鼠心肌缺血再灌注模型制备及其超声分子成像研究  

Establishment of Mouse Model with Myocardial Ischemia-reperfusion and its Ultrasound Molecular Imaging with Microbubbles Targeted to Endothelial P-selectin

作　　者：蔡晶晶[1] 燕翼[1] 杨莉[2] 谢佳佳[1] 胡广全[1] 吴爵非[1] 宾建平[1] 

机构地区：[1]南方医科大学南方医院心内科,广州市510515 [2]南方医科大学南方医院药学部,广州市510515

出　　处：《中国超声医学杂志》2010年第7期581-585,共5页Chinese Journal of Ultrasound in Medicine

基　　金：国家"863"计划基金支持(No.2006AA027Z478)

摘　　要：目的以显微外科技术建立小鼠心肌缺血-再灌注模型,用其评价携抗P-选择素单抗靶向微泡(MBp)的"心肌炎症"超声分子成像效果。方法 30只昆明小鼠随机均分为缺血-再灌注(ischemia-reperfusion,IR)和假手术(sham surgery,SH)组,手术组结扎冠脉前降支15min,再灌注1h。心电图、M型超声、2,3,5-氯化三苯基四氮唑(TTC)和HE染色评价模型构建情况,分别将普通微泡和MBp经静脉注射到实验小鼠体内,评价MBp的超声分子成像效果。结果结扎前降支时前壁心肌呈明显充盈缺损,心电图ST段呈弓背向上抬高。再灌注后充盈缺损消失,ST段降至正常;M型超声检查显示,IR组左室短轴缩短率(LV-%FS)明显低于假手术组(P<0.05);心脏TTC染色无坏死表现,而HE染色提示缺血区心肌存在炎症改变;MBp造影显示前壁心肌呈选择性显影增强,前壁视频强度(video intensity,Ⅵ)明显高于后壁(P<0.01)。增强区域与结扎前降支时的充盈缺损区域高度相关(r=0.95)。结论 MBp可以有效评价心肌缺血再灌注"炎症"损伤,小鼠心肌缺血再灌注模型适宜于超声和其它显像方法的"炎症"分子成像研究。Objective To evaluate the effect on ultrasound molecular imaging of myocardial inflammation with microbubbles targeted to endothelial P selectin （MBp） by establishing a mouse model of myocardial ischemia-reperfusion （IR） with microsurgical techniques. Methods 30 Kunming mice were divided into an IR group [left anterior de scending （LAD） ligation for 15 minutes and reperfusion for 1 hour], and a sham group （sham surgery, SH ）. ECG, M-mode Eehocardiography, HE and 2, 3, 5-Triphenyltetrazolium chloride （TTC） staining were performed, and contrast enhanced ultrasound imaging was acquired after the injection of MBp and regular mierobubbles intravenously. Results An obvious defect in the anterior wall of myocardium and ST segment elevation were detected after LAD ligation. When the reperfusion started, the defect of the anterior wall of rayocardium disappeared and the ST segment returned to normal. Compared with corresponding SH group, LV-% FS obtained from M mode echoeardiography markedly decreased in the IR group （P〈0.05）. There was no obvious necrotic myocardium detected by TTC staining, but HE staining showed inflammation responses existing in the ischemic myocardium. Selective enhancement was demonstrated by targeted imaging with MBp after 1 h of reperfusion in the post-ischemic anterior wall. The ultrasound mo lecular imaging of MBp indicated that the myocardial video intensity （VI） was significantly greater in the post-ischemic anterior risk area compared with the remote posterior non-ischemic territory （P〈0.01）. The contrast enhanced terri- tory after reperfusion was highly correlated with the anterior perfusion defects during LAD occlusion （r = 0.95）. Conclusions MBp can effectively evaluate myocardial IR injury and myocardial inflammation. Myocardial IR with mouse is an ideal model to study molecular imaging of myocardial inflammation for ultrasound and other imaging systems.

关 键 词：心肌缺血再灌注 模型 超声分子成像 P-选择素 微泡 

分 类 号：R542.2[医药卫生—心血管疾病]