Zhao Ling, Ruze Amanguli, Du Guo-Li, Gai Min-Tao, Tang Jing, Gao Xiao-Ming
Department of Cardiology, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asian, First Affiliated Hospital, Clinical Medical Research Institute of Xinjiang Medical University, Urumqi, China.
Xinjiang Key Laboratory of Medical Animal Model Research, Urumqi, China.
PLoS One. 2025 Aug 22;20(8):e0328001. doi: 10.1371/journal.pone.0328001. eCollection 2025.
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.
在小鼠心肌梗死（MI）模型中，心脏破裂的高发生率导致在研究终点前出现大量损失。为不同研究目的选择具有不同损伤程度的动物模型对于心血管研究至关重要。雄性C57小鼠接受缺血/再灌注（I/R）或永久性闭塞（MI）损伤。检测心脏破裂的发生率、心肌损伤程度、炎症反应、左心室（LV）重塑和梗死心肌愈合情况。与MI小鼠相比，早期再灌注（1、2和4小时I/R）完全预防了心脏破裂，而延迟再灌注（12小时和24小时I/R）分别将心脏破裂的发生率显著降低至5.7%和8.6%。在急性期，长时间缺血增加了梗死面积、心肌细胞凋亡以及全身和局部炎症反应。这些变化与MMP-9活性增强和梗死心肌拉伸强度减弱相对应。缺血损伤后，早期再灌注与较小程度的心肌损伤、炎症反应和不良心脏重塑相关，而延迟再灌注组和MI组则表现出严重的心肌损伤和重塑。此外，早期和延迟再灌注在早期愈合阶段均与2型巨噬细胞浸润增加和内皮细胞增殖相关，从而促进梗死心肌的愈合。与MI模型相比，延迟再灌注导致相当程度且严重的心脏重塑，但心脏破裂风险较低。这一特性使其成为心脏缺血研究的可行模型。
