小鼠急性心肌梗死后心脏破裂的性别差异及机制探讨

Gender differences in post-infarct cardiac rupture in a mouse model

目的:探讨小鼠急性心肌梗死(AMI)后心脏破裂的性别差异及其机制。方法:不同性别C57BL小鼠,随机分入假手术组、心肌梗死组。建立AMI模型后,观察不同性别组心脏破裂发生率,并于AMI后第7天行超声和血流动力学检查;应用酶谱法、病理染色及免疫组化方法,分别于AMI后第3天、第7天检测基质金属蛋白酶(MMP-2,MMP-9)活性表达,心肌间质胶原含量(CVF)和类型的变化,检测AMI后第3天炎性细胞浸润程度。结果:1.AMI后雄性组心脏破裂率显著高于雌性组(42.2%与18.4%,P<0.05)。2.与雌性组比较,雄性心肌梗死(MI)组AMI后第3天炎性细胞浸润程度明显增加(P<0.05),第3天、第7天MMP-9表达增加,心肌间质胶原含量较低。3.雄性假手术组平均动脉压(MAP)、左心室收缩压(LVSP)均高于雌性假手术组(P均<0.05),术后第7天时,雄性MI组较雌性MI组表现出显著的左心室扩张、梗死区变薄、心功能障碍以及血流动力学恶化。结论:小鼠AMI后心脏破裂率存在性别差异,雄性明显高于雌性。炎性细胞浸润程度增加、MMP-9活性增高、原有间质胶原过度降解和左心室早期重塑恶化可能是雄性小鼠心脏破裂率增加的重要原因。

Objective： To investigate gender difference in post-infarct cardiac rupture in a mice model and possible mechanisms. Method：C57BL mice in two group： males and females were divided into sham operation group and myocardial infarction（MI） group randomly. Following acute myocardial infarction（AMI） induced by open-chest surgery, the events of cardiac rupture were monitored, the echocardiography and hemodynamics were performed at 7 days after surgery. Zymography, immunohistochemical and pathological staining were used to measure the activity of matrix metalloproteinases（ MMPs）, content of collagen at 3 and 7 days after surgery, and quantitate the inflammatory cells at 3 days after surgery. Result： 1. A significantly higher incidence of cardiac rupture was observed in males than in females（42.2% versus 18.4%, P 〈 0.05）. 2. Males had a significantly higher number of inflammatory cells infiltrating at the infarct border zone at 3 days after surgery（ P 〈 0.05）. MMP-9 activity were higher in males than in females at 3 and 7 days after AMI. The collagen content and the expression of type Ⅰ and Ⅲ collagen were increased in females than in males. 3 .The MAP and LVSP in sham operation group were higher in male mice compare to femals mice（ both P 〈 0.05）. And the severe infarct expansion, worse left ventricular（LV） remodeling and hemodynamics were showed in males compared to females at 7 days after surgery. Conclusion：The cardiac rupture rate during the first week after MI was significantly higher in male mice than in female mice. The mechanisms responsible for this gender- related difference in cardiac rupture were related to more infiltrating inflammatory cells, increased MMP-9 activity, premature collagen degradation, and aggravated early LV remodeling.