两种造模方法建立大鼠冠脉微循环障碍模型比较研究

Comparative study of the establishment of rat coronary microvascular dysfunction models

目的比较月桂酸钠损伤内皮法与微球栓塞法建立冠脉微循环障碍大鼠模型的差异,探索稳定、可用于疾病发病和药物研究的动物模型。方法雄性SD大鼠30只,随机分为假手术组、月桂酸钠组和微球栓塞组,每组10只。大鼠麻醉后开胸,向左心室内注射0.2 mL的月桂酸钠(1 g/L)或栓塞微球(40~120μm,1000个),假手术组注射等体积生理盐水,术后24 h再次麻醉动物测定相关指标处死取材。结果月桂酸钠组可见冠脉微血管血栓形成、心肌细胞损伤,心功能、血流动力学及心肌酶指标与假手术比较未见差异。微球栓塞组可见微球栓塞于冠脉微血管、心肌损伤,左室射血分数、左室缩短率明显降低,左室内压最大上升速率明显降低、肌酸激酶MB同工酶以及乳酸脱氢酶活性明显增加。结论两种造模方法均可以造成冠脉微循环障碍,对大鼠心脏功能有一定影响。微球栓塞法较月桂酸钠法建立的动物模型关键指标更加稳定,可广泛应用于冠脉微循环障碍的发病机制、药物治疗作用等研究。

Objective To explore a rat model for disease pathogenesis and drug discovery research of microvascular dysfunction by comparing two modeling method:sodium laurate injury of endothelium and microsphere embolization.Methods Thirty male SD rats were randomly divided into sham operation,sodium laurate,and microsphere embolization groups with 10 rats in each group.After anesthetizing the rats,their chest was opened.Then,0.2 mL sodium laurate(1 g/L)or embolization microspheres(40~120μm,1×10;)were injected into the left ventricle.The sham operation group was injected with an equal volume of normal saline.Rats were anesthetized to determine relevant indicators and then sacrificed to obtain materials at 24 hours after surgery.Results In the sodium laurate group,coronary microvessel thrombosis and myocardial cell injury were observed,but there were no differences in cardiac functions,hemodynamics,or myocardial enzyme indexes compared with sham operation.However,in the microsphere embolization group,coronary microvessel embolization and myocardial injury were observed.Moreover,left ventricular ejection fraction,left ventricular shortening rate,and the maximum rate of left ventricular pressure were decreased significantly and the activities of creatine kinase MB isoenzyme and lactate dehydrogenase were increased significantly.Conclusions Both modeling method induced coronary microcirculation dysfunction and damaged cardiac functions.The animal model established by microsphere embolization was more reliable than the other method.This method might be widely used to study pathogenesis and drug treatment of coronary microcirculation dysfunction.