经冠状动脉内注射月桂酸钠构建大鼠冠状动脉微栓塞模型

The Establishment of A New Model of Rat Coronary Microthrombosis by Coronary Sodium Laurate Injection

目的建立新的在体大鼠冠状动脉微栓塞模型。方法成年SD大鼠随机分为正常对照组(n=6)、月桂酸钠组(n=54)及微球组(n=27),微球组依所注射微球的数量进一步分为500、1000和3000个次3个亚组(n=9);大鼠麻醉后开胸,夹闭主动脉后经左心室内注射200μg月桂酸钠或42μm的微球达冠状动脉,以注射生理盐水为对照;分别采用病理切片、超声心动图和彩色微粒子测量技术,观察各组大鼠心肌内微血栓和微梗死形成,以及心功能和心肌局部血流量的变化。结果经左心室内注射200μg月桂酸钠后1h,大鼠心肌微小动脉内即有微血栓形成,3h以后达高峰,血栓形成率高达66.4%±18.8%,在此后的12～72h逐渐降低。与微球组相比,所形成的微血栓中不但有血小板及纤维蛋白的聚集,而且还伴有内皮损伤及较严重的炎细胞浸润;二者所形成的微梗死灶皆为锲形呈局灶性分布,但月桂酸钠组梗死部位炎症反应较重。月桂酸钠组所形成的微梗死面积、心功能和心肌局部血流量的下降程度与单次注射1000个微球相似。结论经冠状动脉内注射月桂酸钠可成功构建大鼠冠状动脉微栓塞模型,其最佳剂量和时间点分别为200μg和3h,与机械性的塑料微球栓塞相比,在病理发病机制上比较贴近于临床,可作为冠状动脉微栓塞微循环研究的理想的动物模型。

Aim To establish a new model of coronary microthrombosis model in rats. Methods A total of 87 male Sprague-Dawtey rats were used in this study. Rats were anesthetized with ketamine and derided into sham group （ a = 6）, sodium laurate group （n=54） and microspheres group（n=27）. In sodium laurate（SL） group, 200μg of sodium laurate was injected into the coronary artery while in microspheres {MS） group, different amount of microspheres （42μm in diameter） were injected into the coronary artery, the sham group was injected saline instead. The thrombus induction and consequent of myocardial dysfunction were examined by histopathologieal analyses and non-radiaetive microspheres. Results One hour after SL injection, there is microthrombus in coronary artery and reaches a peak three hours after the ijection（66.4%±18.8%）. Microscopic examination of Carstairs Stain sections （ n = 8） revealed that microthrombi containing fibrin strands obstructed the perforating arteries in the myocardium. Multiple small myocardial infarcts were observed in the heart. Multiple microinfarctlets Were observed and a more severe inflsmmatory reaction was seen in SL group. LVEF was also decreased in SL group which is comparable to the injection of 1000 microspheres. Conclusions Coronary microthrombosis model was auccessfully induced after injection of SL into the coronary artery. The model is useful for the investigation of the pathophysiology of coronary microthrombosis.