不同月龄鼠急性心肌梗死后心室重构和心脏破裂的观察

Effects of aging on ventricnlar remodeling and cardiac rupture after acute myocardial infarction in mice

目的探讨老龄对小鼠急性心肌梗死（AMI）后心室重构心脏破裂的影响。方法老龄和低龄C57BL／6小鼠，随机分为假手术组、心肌梗死组。建立AMI模型后，观察心脏破裂发生率，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、7天检测基质金属蛋白酶-2、-9（MMP-2、MMP-9）活性表达，炎性细胞浸润程度，心肌间质胶原含量（CVF）和类型的变化。结果AMI后老龄组心脏破裂率高于低龄组（38．0％与16．0％，Х^2=6．139，P〈0．05）；第7天时，较低龄组出现明显的梗死区扩张、左心室重构、心功能障碍及血流动力学变化（t=5．754，P〈0．05）。与低龄组比较，老龄AMI组AMI后第3天炎性细胞浸润程度、MMP-9表达明显增加（P〈0．05）。与低龄组比较，老龄组心肌间质胶原含量、Ⅲ型胶原表达增加（P〈0．05）。结论老龄是小鼠AMI后心脏破裂的高危因素，其原因可能与AMI早期炎性细胞浸润程度增加、MMP～9、Ⅲ型胶原过度表达和早期左心室重构恶化有关。

Objective To explore the effects of aging on ventricular remodeling and cardiac rupture after acute myocardial infarction in mice. Methods Male C57BL/6 mice of 3 months and 12 months old were randomly divided into sham operation group and myocardial infarction （MI） group. Following acute myocardial infarction （AMI） modeling induced by open-chest surgery, the events of cardiac rupture were monitored and the echocardiography and hemodynamics were performed on the 7th day after surgery. Zymography, immunohistochemical method and pathological staining were used to measure the activity of matrix metalloproteinases （MMPs）, the content of collagen and the degree of inflammatory cell infiltration on the 3rd and 7th days after surgery, respectively. Results The incidence of cardiac rupture was higher in elderly group than that in young group （38.0% vs. 16.0%, Х^2 =6. 139,P〈0.05）. Compared with young group, significant infarct expansion, left ventricular （LV） remodeling and hemodynamic deterioration were showed in elderly group on the 7th day after surgery （t= 5. 754,P〈0.05）. The degree of inflammatory cell infiltration and the expression of MMP-9 were significantly increased in elderly group on the 3rd day following AMI modeling （P〈 0. 05）, and the collagen content and the expression of type Ⅲ collagen were significantly increased （P〈0.05） compared with young group. Conclusions Aging is a risk factor for post-infarct cardiac rupture in the mice model. The mechanisms which are responsible for this age-related difference of cardiac rupture are related to increasing degree of inflammatory cell infiltration, overexpression of MMP-9 and type Ⅲ collagen and aggravated early LV remodeling.