出 处:《中国组织工程研究》2022年第23期3733-3737,共5页Chinese Journal of Tissue Engineering Research
基 金:山西省自然科学基金面上项目(201801D121299),项目负责人:李庭凯;山西省自然科学基金青年项目(201901D211525),项目负责人:杨钤;山西中医药大学科技创新能力培育计划项目(2019PY-021),项目负责人:杨钤。
摘 要:背景:心肌梗死是冠心病最严重的一种临床类型,抗心肌缺血类药物的研发已成为研究热点。建立合适的动物模型并探讨其病理生理机制,可为新药研发过程中药物的药效学评价提供有效的工具,促进心血管疾病有效治疗药物的开发。目的:评价急性心肌梗死损伤后大鼠的心脏功能、组织形态和心肌细胞超微结构改变。方法:30只雄性SD大鼠随机分为假手术组及模型组,每组15只。模型组采用冠状动脉左前降支结扎法制备心肌梗死模型,假手术组只穿线不结扎。分别在造模后第7,14,28天,心电图观测大鼠Ⅱ导联ST段改变情况;开胸观察心脏大体改变情况;2,3,5-三苯基氯化四氮唑染色法测定心肌梗死面积;苏木精-伊红染色法观察心脏组织病理改变;Masson染色法观察心肌组织纤维化程度;透射电镜观察心肌细胞超微结构改变。结果与结论:①与假手术组比较,模型组大鼠术后7 d心电图可见J点明显抬高,14 d可见Q波的波形增宽、振幅增大;②心脏大体观察可见,模型组大鼠术后7,14 d时左心室肥大,28 d时心脏萎缩;③2,3,5-三苯基氯化四氮唑染色显示,模型组大鼠心梗面积进展性增加;④苏木精-伊红和Masson染色显示,心肌细胞排列紊乱、心肌细胞坏死、炎细胞浸润及纤维增生逐渐加重;⑤透射电镜观察可见,心肌细胞内线粒体肿胀加剧,线粒体嵴数量显著减少;⑥提示SD大鼠心肌梗死模型心脏功能、组织形态以及心肌细胞超微结构改变符合心肌梗死发生、发展规律,可为心肌梗死治疗药物研发提供实验证据。BACKGROUND:Myocardial infarction is the most serious clinical type of coronary heart disease.The development of anti-myocardial ischemia drugs has become a research hotspot.Establishing an appropriate animal model and investigating its pathophysiological mechanism can provide an effective tool for pharmacodynamics evaluation in new drug development and promote the development of anti-myocardial infarction drugs for myocardial infarction.OBJECTIVE:To evaluate the changes of cardiac function,tissue morphology and cardiomyocyte ultrastructure in rats after acute myocardial infarction.METHODS:Thirty male Sprague-Dawley rats were randomly divided into two groups(n=15 per group):a sham surgery group and a model group.Rats in the model group were subjected to ligation of the left anterior descending coronary artery,while in the sham surgery group,the left anterior descending coronary artery was only threaded without ligation.On the 7th,14th,and 28th days after modeling,changes of ST segment in lead II were observed by electrocardiogram,and the general changes of the heart were observed by thoracotomy.Myocardial infarction area was determined by 2,3,5-triphenyltetrazolium chloride staining.Hematoxylin-eosin staining was used for pathological observation of the heart,and Masson staining was adopted for the determination of myocardial fibrosis degree.Moreover,the cardiomyocyte ultrastructure was observed by transmission electron microscope.RESULTS AND CONCLUSION:Compared with the sham surgery group,the results of electrocardiogram showed that the J point was obviously elevated on the 7th day,and the Q wave waveform was broadened and the amplitude was increased on the 14th day.The gross observation of the heart showed that rats in the model group had left ventricular hypertrophy on the 7th and 14th days and cardiac atrophy on the 28th day after operation.The results of 2,3,5-triphenyltetrazolium chloride staining showed myocardial infarction area in the model group was increased progressively.Hematoxylin-eosin and Masson st
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