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方法，观察了人和实验大鼠心肌肥大时心肌细胞和间质细胞的形态学变化及结蛋白的分布。光镜检查显示婴幼儿扩张型心肌病心肌细胞肥大，肌束排列紊乱，间质纤维化。电镜下可见肌原纤维缺乏，粗面内质网和高尔基体增生、肥大。后一项发现可能表明肌细胞中蛋白质合成增加。在法洛四联症患者的心肌中观察到类似的方面，但肌原纤维缺乏。扩张型心肌病肥大心肌细胞结蛋白丝数量增多，排列紊乱。结蛋白免疫标记呈横向和纵向分布， 关于我们 在Z带水平分布于细胞质中。结蛋白排列紊乱的心肌细胞有明显的利钠肽表达，而结蛋白排列正常的心肌细胞则无利钠肽表达。原位杂交显示结蛋白mRNA的表达增加，在右心室的肺动脉结合大鼠的心脏，在那里的利钠肽或α-骨骼肌肌动蛋白的mRNA也表达。在扩张型心肌病、扩张期肥厚型心肌病、心肌梗死和先天性心脏病伴心室扩张的心肌组织中，间质成纤维细胞增生，α-平滑肌肌动蛋白免疫反应阳性。它们还显示了非肌肉肌球蛋白重链的胚胎亚型的阳性反应性。这些细胞的超微结构包括纤维插入位点、丰富的肌动蛋白丝和不连续的基底膜，表明这些细胞是肌成纤维细胞。这些结果表明，肥大的心肌细胞表现出各种形态学变化的转化和间质成纤维细胞也转化在婴儿，儿童和成人的病变心脏的心肌组织。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