Li F, Wang X, Capasso J M, Gerdes A M
Department of Anatomy and Structural Biology, University of South Dakota, School of Medicine, Vermillion 57069, USA.
J Mol Cell Cardiol. 1996 Aug;28(8):1737-46. doi: 10.1006/jmcc.1996.0163.
The switch from myocyte hyperplasia to hypertrophy occurs during the early postnatal period. The exact temporal sequence when cardiac myocytes cease dividing and become terminally differentiated is not certain, although it is currently believed that the transition takes place gradually over a 1-2-week period. The present investigation has characterized the growth pattern of cardiac myocytes during the early postnatal period. Cardiac myocytes were enzymatically isolated from the hearts of 1, 2, 3, 4, 6, 8, 10, and 12-day-old rats for the measurements of binucleation, cell volume and myocyte number. Almost all myocytes were mononucleated and cell volume remained relatively constant during the first 3 days of age. Increases in cell volume and binucleation of myocytes were first detected at day 4. Myocyte volume increased 2.5-fold from day 3 to day 12 (1416 +/- 320 compared to 3533 +/- 339 microns 3). The percentage of binucleated myocytes began to increase at day 4 and proceeded at a high rate, reaching the adult level of approximately 90% at day 12. Myocyte number increased 68% during the first 3 days (from 13.6 +/- 3.5 x 10(6) at day 1 to 22.9 +/- 5.6 x 10(10) at day 3) and remained constant thereafter. To confirm that no further myocyte division exists after 4 days, bromodeoxyuridine (Brdu) was administered to 4-day-old rats and the fate of DNA-synthesizing myocytes was examined 2 h and 2, 4, 6 and 8 days after Brdu injection. About 12% of myocytes were labeled with Brdu at 2 h and all were mononucleated at that time. Gradually, these Brdu-labeled myocytes became binucleated. However, the percentage of labeled myocytes in all groups was identical, indicating that DNA-synthesizing myocytes were becoming binucleated without further cell division after 4 days of age. Within 8 days after injection, approximately 82% of total labeled myocytes were binucleated, while the others remained mononucleated. Sarcomeric alpha-actinin was fully disassembled in dividing myocytes of 2-day-old rats, while typical alpha-actinin striations were present in dividing myocytes of 4-day-old rats. The results from this study suggest that a rapid switch from myocyte hyperplasia to hypertrophy occurs between postnatal day 3 and 4 in rat hearts.
心肌细胞从增生向肥大的转变发生在出生后早期。虽然目前认为这种转变在1 - 2周的时间内逐渐发生，但心肌细胞停止分裂并最终分化的确切时间顺序尚不确定。本研究对出生后早期心肌细胞的生长模式进行了表征。从1、2、3、4、6、8、10和12日龄大鼠的心脏中酶解分离心肌细胞，用于测量双核化、细胞体积和心肌细胞数量。几乎所有的心肌细胞在出生后的前3天都是单核的，并且细胞体积保持相对恒定。在第4天首次检测到心肌细胞体积增加和双核化。从第3天到第12天，心肌细胞体积增加了2.5倍（分别为1416±320立方微米和3533±339立方微米）。双核心肌细胞的百分比在第4天开始增加，并以较高的速率持续增加，在第12天达到约90%的成年水平。心肌细胞数量在最初3天增加了68%（从第1天的13.6±3.5×10⁶个增加到第3天的22.9±5.6×10⁶个），此后保持恒定。为了证实4天后不再有心肌细胞分裂，给4日龄大鼠注射溴脱氧尿苷（Brdu），并在注射Brdu后2小时以及2、4、6和8天检查DNA合成心肌细胞的命运。在2小时时，约12%的心肌细胞被Brdu标记，此时所有细胞均为单核。逐渐地，这些被Brdu标记的心肌细胞变成双核。然而，所有组中标记心肌细胞的百分比是相同的，这表明4日龄后DNA合成心肌细胞在没有进一步细胞分裂的情况下变成双核。注射后8天内，约82%的总标记心肌细胞为双核，而其他细胞仍为单核。在2日龄大鼠的分裂心肌细胞中，肌节α-肌动蛋白完全解体，而在4日龄大鼠的分裂心肌细胞中存在典型的α-肌动蛋白条纹。本研究结果表明，大鼠心脏在出生后第3天和第4天之间发生了从心肌细胞增生到肥大的快速转变。
