Dalla Libera Luciano, Ravara Barbara, Volterrani Maurizio, Gobbo Valerio, Della Barbera Mila, Angelini Annalisa, Danieli Betto Daniela, Germinario Elena, Vescovo Giorgio
Internal Medicine II, Ospedale S. Bortolo, Viale Rodolfi 37, 36100 Vicenza, Italy.
Am J Physiol Cell Physiol. 2004 Jan;286(1):C138-44. doi: 10.1152/ajpcell.00114.2003. Epub 2003 Sep 17.
Muscle atrophy is a determinant of exercise capacity in heart failure (CHF). Myocyte apoptosis, triggered by tumor necrosis factor-alpha (TNF-alpha) or its second messenger sphingosine (SPH), is one of the causes of atrophy. Growth hormone (GH) improves hemodynamic and cardiac trophism in several experimental models of CHF, but its effect on skeletal muscle in CHF is not yet clear. We tested the hypothesis that GH can prevent skeletal muscle apoptosis in rats with CHF. CHF was induced by injecting monocrotaline. After 2 wk, 2 groups of rats were treated with GH (0.2 mg.kg(-1).day(-1) and 1.0 mg.kg(-1).day(-1)) subcutaneously. A third group of controls had saline. After 2 additional weeks, rats were killed. Tibialis anterior cross-sectional area, myosin heavy chain (MHC) composition, and a study on myocyte apoptosis and serum levels of TNF-alpha and SPH were carried out. The number of apoptotic nuclei, muscle atrophy, and serum levels of TNF-alpha and SPH were decreased with GH at high but not at low doses compared with CHF rats. Bcl-2 was increased, whereas activated caspases and bax were decreased. The MHC pattern in GH-treated animals was similar to that of controls. Monocrotaline slowed down both contraction and relaxation but did not affect specific tetanic force, whereas absolute force was decreased. GH treatment restored contraction and relaxation to control values and brought muscle mass and absolute twitch and tetanic tension to normal levels. These findings may provide an insight into the therapeutic strategy of GH given to patients with CHF to improve exercise capacity.
肌肉萎缩是心力衰竭（CHF）患者运动能力的一个决定因素。由肿瘤坏死因子-α（TNF-α）或其第二信使鞘氨醇（SPH）触发的心肌细胞凋亡是萎缩的原因之一。生长激素（GH）在几种CHF实验模型中可改善血流动力学和心脏营养，但它对CHF患者骨骼肌的影响尚不清楚。我们检验了GH可预防CHF大鼠骨骼肌凋亡的假说。通过注射野百合碱诱导CHF。2周后，两组大鼠皮下注射GH（0.2mg·kg-1·天-1和1.0mg·kg-1·天-1）。第三组为对照组，注射生理盐水。再过2周后，处死大鼠。对胫骨前肌横截面积、肌球蛋白重链（MHC）组成进行检测，并研究心肌细胞凋亡以及TNF-α和SPH的血清水平。与CHF大鼠相比，高剂量而非低剂量的GH可减少凋亡细胞核数量、肌肉萎缩以及TNF-α和SPH的血清水平。Bcl-2增加，而活化的半胱天冬酶和bax减少。GH治疗组动物的MHC模式与对照组相似。野百合碱使收缩和舒张均减慢，但不影响强直比肌力，而绝对肌力降低。GH治疗可使收缩和舒张恢复至对照值，并使肌肉质量、绝对抽搐和强直张力恢复至正常水平。这些发现可能为给予CHF患者GH以改善运动能力的治疗策略提供思路。
