›› 2007, Vol. 27 ›› Issue (3): 149-154.

• 论文 •    下一篇

细胞移植研究用大鼠心肌梗死动物模型的建立

  

  1. 1.同济大学附属东方医院,心胸外科,上海 200120;2.同济大学附属东方医院,病理科,上海 200120
  • 收稿日期:2007-04-25 出版日期:2007-03-31 发布日期:2007-03-31
  • 基金资助:
    国家自然科学基金资助项目(30471719),上海市浦东新区优秀学科带头人项目(PWR2004-1)和上海市教委曙光计划(04SG25)。

Establishment of a Standard Acute Myocardial Infarction Model for Cellular Transplantation Research in Rats

  1. 1. Department of Cardiovascular and Thoracic Surgery,2. Department of Pathology, East Hospital Affiliated Tongji University, Shanghai 200120, China
  • Received:2007-04-25 Online:2007-03-31 Published:2007-03-31

摘要: 目的 探索大鼠左冠状动脉前降支(LAD)结扎处理的适宜方法,建立适合细胞移植研究的稳定、可靠的急性心肌粳死(AMI)动物模型.方法 14只SD大鼠麻醉满意后,在动物呼吸机的支持下打开胸腔,于LAD中上1/3处结扎,并在结扎前后通过多外围设备转接器(MPA)生物信号分析系统连续监测心电图;4周后再次开胸取出心脏,利用Langendorff离体心脏灌流MPA系统检测左室收缩压(LVSP)左室舒张末压(LVEDP)左心室内压力上升及下降的最大变化速率(±dp/dtmax)等左室心功能指标;并测定心肌组织病理形态学、心肌梗死面积(MIS)等评价AMI模型的建立情况.另选仅开、关胸后存活的10只大鼠作为对照组.结果 造模成功率为71.43%(10/14);心电图动态监测在LAD结扎后出现ST-T抬高的融合波,30min后可见Q波;4周后Langendorff离体心脏灌流MPA系统检测显示LVSP、±dp/dtmax等指标较对照组显著降低,LVEDP则明显升高(P<0.01);病理组织切片可见结扎区域心肌纤维排列紊乱、肌丝断裂溶解、细胞核固缩甚至碎裂、间质充血水肿、有炎性细胞浸润、坏死心肌被纤维组织取代:且MIS变化较恒定(44.38%±8.04%).结论 通过结扎LAD,于4周后能够形成梗死部位和MIS稳定的AMI模型,适合于移植细胞再生修复梗死心肌的研究.

关键词: 心肌梗塞, 细胞移植, 动物模型, 心肌梗死面积, 心功能

Abstract: Objective To explore the feasibility of establishment of acute myocardial infarction (AMI) models induced by occlusion of left anterior descending coronary artery (LAD), which provide a reliable model for the study of repair myocardial infarction by cellular transplantation in rat. Methods Fourteen adult Sprague-Dawley (SD) rats with respirator were established by ligating the middle-proximal 1/3segment of left anterior descending coronary artery (LAD) in AMI model group. Continuous electrocardiographic monitoring were performed both before the LAD ligating and after the LAD ligated by multiple peripheral adapter (MPA) multichannel physiologic recorder system. The cardiac function indicated by these parameters of left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP) and 士 dp/dtmax were observed by multipurpose polygraph of langendorff perfusion of the isolated heart methods, and their pathological morphology, myocardial infarction size (MIS) and mortality were detected and analyzed four weeks after LAD occlusion to see whether there were any tissue necrosis and its extension. Other ten adult SD rats without ligating coronary artery as control group. Results The survival rate of the treated rats was 71.43% (10/14) beyond four weeks. After LAD ligation, electrocardiogram displayed ST elevated continuously immediately and pathologic Q wave after ligating 30 min. Pathologic examination suggested myofibers chaotically arranged, myofilament ruptured or lysed, nuclei pyknosis and fragmentation, interstitial hyperemia and edema, infiltration of inflammatory cells, necro-myocardium were superseded by fibrous tissue. Meanwhile, the cardiac function observation indicated by these parameters of LVSP、LVEDP and 土dp/dtmax descend markedly in LAD occlusion rats after ligating four weeks late. MIS were invariableness in AMI model group (44.38% 士 8.04。/。). Conclusion A standard rat AMI model could be created by surgical ligation of LAD, and the model would be suitable for the research on cellular transplantation.

Key words: Acute myocardial infarction, Cellular transplantation, Animal models, Myocardial infarction size, Cardiac function