A study on the mechanism of transformation of the hypertrophied myocardium in infants, children and adults

本研究采用组织病理学、免疫组织化学和分子生物学等方法，观察人和实验大鼠病变心脏肥大肌细胞和间质细胞的形态变化和desmin分布。婴幼儿扩张型心肌病的光镜检查显示心肌细胞肥大、肌束紊乱、间质纤维化。电镜显示肌原纤维缺乏，线粒体分裂，粗面内质网和高尔基体增生。后一种结果可能提示肌细胞中蛋白质合成的增加。在法洛四联症患者心肌中，除了肌原纤维缺乏外，观察到类似的方面。扩张型心肌病的促丝蛋白数量增加，其特征是在肥厚的肌细胞中排列紊乱。在这些细胞的细胞质中，Desmin免疫标记主要分布在Z带水平。特异蛋白排列紊乱的肌细胞有明显的利钠肽表达，而特异蛋白排列正常的肌细胞有明显的利钠肽表达。原位杂交显示肺动脉结合大鼠心脏右心室desmin mRNA表达增加，其中利钠肽或α -骨骼肌肌动蛋白mRNA也有表达。扩张型心肌病、扩张期肥厚型心肌病、心肌梗死和先天性心脏病伴室性扩张的心肌组织间质成纤维细胞增殖对α -平滑肌肌动蛋白呈阳性免疫反应。他们还发现胚胎非肌球蛋白重链异构体有阳性反应。这些细胞的超微结构包括纤维插入部位、丰富的肌动蛋白丝和不连续的基底膜，提示它们是肌成纤维细胞。这些结果表明，在婴儿、儿童和成人的病变心脏心肌组织中，肥大的肌细胞在转化过程中表现出各种形态变化，间质成纤维细胞也发生转化。少

This study was designed to investigate the the morphological change and the desmin distribution in the hypertrophied myocytes and interstitial cells in the diseased heart of human and experimental rats by the methods of histopathology, immunohistochemistry and molecular biology. Light-microscopical examination revealed myocyte hypertrophy, disarrangement of muscle bundle and interstitial fibrosis in dilated cardiomyopathy of infants and children. Electronmicroscopy revealed scarcity of myofibrils, mitochondriosis and proliferation of rough-surfaced endoplasmic reticulum and Golgi apparatus. The latter findings may suggest an increase in protein synthesis in the myocyte. Similar aspects except for scarcity of myofibrils were observed in the myocardium from patients with Tetralogy of Fallot. Desmin filaments were increased in number and characterized by a disordered arrangement in the hypertrophied myocytes in dilated cardiomyopathy. Desmin immunolabeling was transversely and longitudina … More ly distributed at the Z band level in the cytoplasm of these cells. Myocytes with disordered arrangement of desmin showed distinct expression of natriuretic peptides, while negative expression of them was revealed in the myocytes with normally arranged desmin. In situ hybridization showed increase in expression of desmin mRNA in the right ventricle of the pulmonary artery-binding rat heart, where mRNA of natriuretic peptides or alpha-skeletal muscle actin was also expressed. Interstitial fibroblastic cells proliferated in the myocardial tissue in dilated cardiomyopathy, dilated-phase hypertrophic cardiomyopathy, myocardial infarction and congenital heart disease with ventricular dilatation showed positive immunoreactivity for alpha-smooth muscle actin. They also revealed positive reactivity for embryonic isoform of non-muscle myosin heavy chain. These cells are suggested to be myofibroblasts by the ultrastructural aspects including filament insersion site, abundant actin filaments and discontinuous basement membranes. These results indicate that hypertrophied myocytes show various morphological changes with transformation and interstitial fibroblastic cells also transform in the myocardial tissue of the diseased heart in infants, children and adults. Less