微创条件下小鼠心肌梗死模型建立的研究

Establishment of chronic myocardial infarction model with minimally invasive methods in mice

目的:微创条件下建立小鼠慢性心肌梗死模型,为研究干细胞移植治疗对心肌梗死后心脏的影响提供模型。方法:将70只小鼠随机分为6组,5个手术组和1个假手术组。手术组小鼠于左侧胸骨旁0.8 cm处切开一长约1 cm的切口,钝性分离暴露肋间隙。将心脏从第4、5肋间隙挤出,用5号丝线结扎左心耳和动脉圆锥下的左前降支,放回胸腔后缝合胸壁皮肤。假手术组小鼠左前降支动脉不结扎,余操作同手术组。观察手术后心脏大体形态,术后30 min、3、5、7、14和21 d的心电图及心脏组织的病理学变化。结果:左心室梗死区呈暗褐色,经固定液灌流后梗死区呈白色透明状。术后30 min内,心电图上ST段弓背向上抬高超过0.2 mV。术后3、5、7、14和21 d,心电图被病理性Q波代替,ST段低平。苏木精-伊红染色显示,术后3、5 d有大量的炎细胞浸润,心肌细胞不完整,以术后5 d更明显。术后7 d、14 d梗死区心肌纤维断裂溶解,心肌细胞坏死,少量炎性细胞浸润,术后21 d梗死区被纤维组织所代替。结论:以微创手术建立小鼠心肌梗死模型为一种渐进性、慢性过程,该方法操作时间短、动物耐受性好、可重复性强。

AIM： To establish a chronic myocardial infarction model with minimally invasive methods in mouse and to provide a model for observing effects of stem cell transplantation on infarcted heart. METHODS： Seventy mice were randomly divided into six groups： five operation groups and one sham operation group. A 1-cm incision was made 0.8 cm away from the left side of sternum with the operated mice group. The fourth and fifth intercostal space was exposed via blunt dissection and the heart was squeezed out through the intercostal space. The left anterior descending coronary artery was ligated using #5 suture, and the heart was then returned to the chest. The incision was sutured in a purse-string manner. The left anterior descending coronary artery of mice of the sham operation group did not ligate. General shapes, electrocardiogram and morphologic changes of the heart were observed postoperatively in each group. RESULTS ： The color of the infarct area was dark brown, which became translucent after perfusion of a fixative solution. During the first 30 min after LAD ligation, elevation of ECG ST-segment was 〉0. 2 mV. Pathologic Q wave and lowering ST-segment appeared 3 days after infiltration of many inflammatory cells and broken cardiomyocytes ligation. Pathological section suggested 3 or 5 days after ligation. The changes were more obvious 5 days after ligation. Ruptured or lysed myofibers, necrosis of myocardiac cells, and infiltration of fewer inflammatory cells were observed 7 or 14 days after the ligation. The infarcted area was replaced by fibrous tissue 21 days after ligation. CONCLUSION： The model of myocardial infarc- tion in mice is successfully established via a minimally invasive method. The model we introduced in this experiment is time-saving, stable and easily repeatable.