Lu Lu, Mei Dan Feng, Gu An-Guo, Wang Su, Lentzner Benjamin, Gutstein David E, Zwas Donna, Homma Shunichi, Yi Geng-Hua, Wang Jie
Division of Circulatory Physiology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York City, NY 10032, USA.
J Appl Physiol (1985). 2002 Apr;92(4):1524-30. doi: 10.1152/japplphysiol.00405.2001.
The cardiac sarcoplasmic reticulum calcium-ATPase (SERCA2a), Na+/Ca2+ exchanger (NCX1), and ryanodine receptor (RyR2) are proteins involved in the regulation of myocyte calcium. We tested whether exercise training (ET) alters those proteins during development of chronic heart failure (CHF). Ten dogs were chronically instrumented to permit hemodynamic measurements. Five dogs underwent 4 wk of cardiac pacing (210 beats/min for 3 wk and 240 beats/min for the 4th wk), whereas five dogs underwent the same pacing regimen plus daily ET (5.1 +/- 0.3 km/h, 2 h/day). Paced animals developed CHF characterized by hemodynamic abnormalities and reduced ejection fraction. ET preserved resting hemodynamics and ejection fraction. Left ventricular samples were obtained from all dogs and another five normal dogs for mRNA (Northern analysis, band intensities normalized to glyceraldehyde-3-phosphate dehydrogenase) and protein level (Western analysis, band intensities normalized to tubulin) measurements. In failing hearts, SERCA2a was decreased by 33% (P < 0.05) and 65% (P < 0.05) in mRNA and protein level, respectively, compared with normal hearts; there was only an 8.6% reduction in mRNA and a 32% reduction in protein in exercised animals (P < 0.05 from CHF). mRNA expression of NCX1 increased by 44% in paced-only dogs compared with normal (P < 0.05) but only by 22% in trained dogs (P < 0.05 vs. CHF); protein level of NCX1 was elevated in paced-only dogs (71%, P < 0.05) but partially normalized by ET (33%, P < 0.05 from CHF). RyR2 was not altered in any of the dogs. In conclusion, long-term ET may ameliorate cardiac deterioration during development of CHF, in part via normalization of myocardial calcium-handling proteins.
心肌肌浆网钙ATP酶（SERCA2a）、钠/钙交换体（NCX1）和兰尼碱受体（RyR2）是参与调节心肌细胞钙的蛋白质。我们测试了运动训练（ET）在慢性心力衰竭（CHF）发展过程中是否会改变这些蛋白质。十只狗被长期植入仪器以进行血流动力学测量。五只狗接受了4周的心脏起搏（第1至3周为每分钟210次搏动，第4周为每分钟240次搏动），而另外五只狗接受相同的起搏方案并加上每日ET（5.1±0.3公里/小时，每天2小时）。接受起搏的动物出现了以血流动力学异常和射血分数降低为特征的CHF。ET维持了静息血流动力学和射血分数。从所有狗以及另外五只正常狗身上获取左心室样本，用于mRNA（Northern分析，条带强度以甘油醛-3-磷酸脱氢酶进行标准化）和蛋白质水平（Western分析，条带强度以微管蛋白进行标准化）测量。与正常心脏相比，在衰竭心脏中，SERCA2a的mRNA水平和蛋白质水平分别降低了33%（P<0.05）和65%（P<0.05）；在接受运动训练的动物中，mRNA仅降低了8.6%，蛋白质降低了32%（与CHF相比，P<0.05）。与正常狗相比，仅接受起搏的狗中NCX1的mRNA表达增加了44%（P<0.05），但在接受训练的狗中仅增加了22%（与CHF相比，P<0.05）；仅接受起搏的狗中NCX1的蛋白质水平升高（71%，P<0.05），但ET使其部分恢复正常（与CHF相比，降低了33%，P<0.05）。在任何一只狗中，RyR2均未发生改变。总之，长期ET可能会改善CHF发展过程中的心脏恶化，部分原因是通过使心肌钙处理蛋白恢复正常。
