心力衰竭力学机制研究

The synchronous mechanism of myocardial regeneration-cell disintegration-myocardial fibrosis and its relationship with heart failure

目的观察成年猪急性心肌梗死后心肌细胞再生现象和新生心肌细胞命运,探讨心肌再生后心肌纤维化的机制,及其与心力衰竭发生、发展、转归的关系。方法中国小型猪9只,体质量18~20 kg。实验组(n=6)结扎冠状动脉左前降支(LAD)上的等流量点,对照组(n=3)不进行任何手术操作。术中监测左心室不同部位血流动力学指标。4周后取出心脏标本,将左心室分成17段,4%多聚甲醛固定1周,进行HE、PTAH、Ki-67-DAB单染色联合α-sarcomeric-actin-DAB双重染色,进行病理学及免疫组织化学观察。结果LAD结扎4周后,左心室17段心肌内均可发现大小不等梗死灶,左心室腔近心端与远心端收缩期存在显著压力差。此压力差是心肌张力的主要来源,也是加重心力衰竭的关键因素。LAD结扎4周后梗死区域周边有大量新生心肌细胞,与原有成熟心肌细胞有直接纤维延续。梗死心肌周边大量新生的心肌细胞解体,心肌纤维断裂,细胞结构消失,细胞核散落于纤维化的心肌组织中。结论急性心肌梗死后,梗死区域周边有大量新生心肌细胞,在心肌张力作用下心肌细胞再生、细胞解体、心肌纤维化同步进行,并形成心力衰竭恶性循环。

Objective To observe the cardiomyocytes regeneration after myocardial infarction in Chinese small pigs,analyze the mechanism of myocardial fibrosis after myocardial regeneration.Methods Nine Chinese small pigs,weight 18-20 kg,6 pigs in the experimental group(to ligate LAD at the equal blood flow point),and 3 in the control group(no any operation was performed).Monitor the hemodynamics of the left ventricle.Cardiac specimens were taken after 4 weeks of LAD ligation,the left ventricle was divided into 17 segments,and fixed in 4%paraformaldehyde for 1 week.Hematoxylin-Eosin/(HE)staining,PTAH、Ki-67-DAB andα-sarcomeric-actin-DAB staining for pathological observation.Results Four weeks of LAD ligation,different range of infarct size could be found in all the 17 segment of left ventricle.There was significant systolic pressure difference between the proximal and distal part in the left ventricular cavity.After 4 weeks of LAD ligation,there were a large number of new cardiomyocytes around the infarction area,which connected with the original mature cardiomyocytes directly.Large number of disassembled cardiomyocytes in the infarcted area and myocardial fibers were broken,cell structure disappeared,and nuclei were scattered in fibrotic tissues.Conclusion New cardiomyocytes after myocardial infarction were derived from the mature cardiomyocytes.Myocardial regeneration,cell disintegration,and myocardial fibrosis were performed synchronously under the influence of myocardial tension.