Ameredes B T, Daood M J, Watchko J F
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh; and Magee Womens Research Institute, Pittsburgh, PA, 15261, USA.
J Mol Cell Cardiol. 1998 Aug;30(8):1525-33. doi: 10.1006/jmcc.1998.0718.
Growth hormone (GH) was administered (1 mg/day, i.p., 7.5 months) to male Fischer 344 rats, in conjunction with refeeding (RF) after chronic undernutrition (UN), from middle age (17 months old) to senescence (24.5 months old), during which cardiac myosin heavy chain (MHC) profiles were determined by gel-electrophoresis. At 17 months of age, respective MHC-alpha and -beta composition was 74 and 26% in the right ventricle (RV), and 58 and 42% in the left ventricle (LV), of ad libitum-fed controls. At 24.5 months of age, MHC profiles of controls were shifted toward the MHC-beta isoform in both RV (alpha=53%, beta=47%) and LV (alpha=40%, beta=60%), indicating a significant effect of aging on MHC composition in both ventricles. At 17 months of age, 7.5 months of UN likewise resulted in a shift toward the MHC-beta isoform in both RV (alpha=31%, beta=69%) and LV (alpha=22%, beta=78%) as compared to controls, indicating a significant effect of UN in both ventricles. Continued UN into senescence maintained these altered profiles in both ventricles, at 24.5 months of age (RV: alpha=35%, beta=65%; LV: alpha=24%, beta=76%). RF+GH administered from middle age into senescence restored the MHC composition in both ventricles (RV: alpha=57%, beta=43%; LV: alpha=43%, beta=57%), to that of the controls. RF, alone, likewise reversed ventricular MHC composition toward that of MHC-alpha, but appeared to overcompensate (RV: alpha=67%, beta=33%; LV: alpha=46%, beta=54%), surpassing the control and RF+GH profiles, significantly in the RV. These data suggest that GH is a modulator of restoration of cardiac MHC composition, when RF is administered to counter the effects of chronic UN, in the aging rat heart.
将生长激素(GH)以1毫克/天的剂量腹腔注射给雄性Fischer 344大鼠,持续7.5个月,同时在中年(17月龄)至衰老(24.5月龄)期间,对长期营养不良(UN)后的大鼠进行再喂养(RF),在此期间通过凝胶电泳测定心肌肌球蛋白重链(MHC)谱。在17月龄时,随意进食的对照组右心室(RV)中MHC-α和-β的各自组成分别为74%和26%,左心室(LV)中为58%和42%。在24.5月龄时,对照组的MHC谱在RV(α=53%,β=47%)和LV(α=40%,β=60%)中均向MHC-β异构体偏移,表明衰老对两个心室的MHC组成有显著影响。在17月龄时,与对照组相比,7.5个月的UN同样导致RV(α=31%,β=69%)和LV(α=22%,β=78%)中向MHC-β异构体偏移,表明UN对两个心室有显著影响。持续到衰老期的UN使两个心室在24.5月龄时保持这些改变的谱型(RV:α=35%,β=65%;LV:α=24%,β=76%)。从中年到衰老期给予RF+GH可使两个心室的MHC组成恢复到对照组水平(RV:α=57%,β=43%;LV:α=43%,β=57%)。单独给予RF同样使心室MHC组成向MHC-α方向逆转,但似乎过度补偿了(RV:α=67%,β=33%;LV:α=46%,β=54%),在RV中显著超过了对照组和RF+GH的谱型。这些数据表明,当给予RF以对抗慢性UN的影响时,GH是衰老大鼠心脏中心肌MHC组成恢复的调节剂。