一种新型apoE-/-小鼠动脉粥样硬化和心肌梗死双模型的建立

Establishment of a Novel Model of Atherosclerosis and Myocardial Infarction in apoE-/- Mice

目的对apoE-/-小鼠给予高脂饮食和开胸结扎左前降支(LAD)干预,探索建立一种新型同一生物体内动脉粥样硬化(AS)和急性心肌梗死(AMI)并存的小鼠双模型。方法选择30只雄性6周龄apoE-/-小鼠,高脂饮食饲养;5只普通饮食饲养作为对照。第12周时异氟烷气体麻醉下,开胸采用挤压法暴露心脏,直视下快速结扎LAD中段,体表心电图记录心电学变化;继续饲养3周后处死动物并取材,评估心肌梗死和动脉粥样硬化的病理改变。采用心肌Evans′blue-TTC染色观察心肌梗死范围,Masson染色观察心肌梗死病理变化;主动脉血管段行油红O染色及HE染色,观察动脉粥样硬化斑块形成。结果术中见结扎点下方心肌变白,心电图提示ST段和J点抬高,符合急性心肌梗死临床特征。心肌Evans′blue-TTC染色可见明显的白色梗死区域,Masson染色可见心肌梗死区凝固性坏死伴大量纤维组织形成,符合心肌梗死的典型病理改变。直视条件下主动脉血管段可见大量斑块形成,油红O染色见明显橘红色染色区域,HE染色可见斑块内泡沫细胞脂质沉积,证实apoE-/-小鼠结合高脂饮食可形成明显的动脉粥样硬化病理改变。结论首次报道一种新型apoE-/-小鼠动脉粥样硬化和心肌梗死双模型的建立,两种病理状态的并存更为接近临床心血管疾病的发病特点,为冠心病发病机制的研究和药物干预评估提供平台。

Objective To establish a novel composite model of atherosclerosis （AS） and acute myocardial infarction （AMI） in apoE /mice by high fat diet and thoracotomy ligation of left anterior descending branch（LAD）.Methods Thirty 6 week old male apoE /mice were selected and fed with high fat diet.Five apoE / mice fed with ordinary diet were used as controls.At 12 weeks,underisoflurane gas anesthesia,the chest was exposed by extrusion thoracotomy method.The middle left anterior descending （LAD） coro -nary artery was rapidly ligated.The change of electrocardiology was recorded by surface electrocardiogram （ECG）.Animals were sac -rificed 3 weeks later and the pathologic changes of myocardial infarction and atherosclerosis were assessed.The myocardial infarctedarea was observed by Evans ′ blue TTC staining.Masson staining was used to observe the pathological changes of myocardial infarc -tion.The aortic vascular segment was stained with oil red O and Hematoxylin and Eosin （HE） staining,and the formation of atheroscle -rotic plaque was observed.Results During the operation,the myocardium under the ligation point became white due to ischemia.TheECG showed ST segment and J point elevation,which was consistent with the clinical features of AMI.Myocardial Evans ′blue TTCstaining showed obvious white infarct area.Masson staining showed coagulative necrosis with massive fibrous tissue formation in myocardial infarction area,which was consistent with the typical pathological changes of myocardial infarction.The macroscopic observa -tion showed a large number of plaque formation in the aortic vascular segment.HE staining showed that the foam cells with lipid depo -sition were observed in the plaque.It was confirmed that the apoE / mice combined with the high fat diet could form the obviouspathological changes in atherosclerosis.Conclusion The establishment of a new model of apoE / mice with atherosclerosis andmyocardial infarction was first reported.The coexistence of the two pathological states is closer to the pathogenesis of clinical cardio -vascular disease.It will provide a platform for the research on coronary pathogenesis and drug intervention assessment.