Primer sequences for real-time qPCR.

High incidence of cardiac rupture in murine myocardial infarction (MI) model leads to a substantial loss before the study end-point. Selecting animal models with varying degrees of injury for different research purposes is crucial for cardiovascular research. Male C57 mice were subjected to ischemia/reperfusion (I/R) or permanent occlusion (MI) injury. The incidence of cardiac rupture, degree of myocardial injury, inflammatory responses, left ventricular (LV) remodeling and infarct myocardium healing were examined. Compared to MI mice, early reperfusion (1, 2 and 4h I/R) completely prevented cardiac rupture, while delayed reperfusion (12h and 24h I/R) significantly reduced incidence of cardiac rupture to 5.7% and 8.6%, respectively. In the acute phase, prolonged ischemia increased infarct size, myocyte apoptosis, and both systemic and regional inflammatory responses. These changes correspond to enhanced MMP-9 activity and a weakening of the tensile strength of the infarcted myocardium. Following ischemic insult, early reperfusion was associated with less extent of myocardial injury, inflammatory response and adverse cardiac remodeling, whereas, delayed reperfusion and MI groups exhibited severe myocardial damage and remodeling. Furthermore, both early and delayed reperfusion were associated with increased infiltration of type 2 macrophages and proliferation of endothelial cells during the early healing phase, thereby facilitating healing of the infarct myocardium. Delayed reperfusion resulted in a comparable and substantial degree of cardiac remodeling but with a lower risk of cardiac rupture in comparison with MI model. This feature makes it a feasible model for cardiac ischemia research.小鼠心肌梗死（myocardial infarction, MI）模型的心脏破裂发生率极高，常导致研究终点前出现大量动物丢失。针对不同研究需求选择损伤程度各异的动物模型，对于心血管研究而言至关重要。本研究对雄性C57小鼠实施缺血再灌注（ischemia/reperfusion, I/R）造模或永久性冠状动脉结扎（即心肌梗死模型，MI），随后对各组小鼠的心脏破裂发生率、心肌损伤程度、炎症反应水平、左心室（left ventricular, LV）重构情况以及梗死心肌愈合状态进行了检测。与MI模型小鼠相比，早期再灌注组（缺血1、2、4小时后实施再灌注的I/R组）可完全阻断心脏破裂发生；而延迟再灌注组（缺血12、24小时后实施再灌注的I/R组）则可将心脏破裂发生率分别显著降至5.7%与8.6%。在急性期，缺血时长延长会增大梗死面积、加重心肌细胞凋亡，并加剧全身与局部炎症反应。上述变化与基质金属蛋白酶9（MMP-9）活性升高、梗死心肌抗拉强度降低存在显著相关性。缺血损伤后实施早期再灌注，可减轻心肌损伤、炎症反应与不良心脏重构程度；而延迟再灌注组与MI模型组则表现出更为严重的心肌损伤与心脏重构。此外，在梗死早期愈合阶段，早期与延迟再灌注组均出现2型巨噬细胞浸润增多与内皮细胞增殖现象，进而促进梗死心肌的愈合。与MI模型相比，延迟再灌注模型的心脏重构程度同样显著，但心脏破裂风险更低，这一特性使其成为心脏缺血相关研究的可行动物模型。