COMPARISON OF THE EFFECTS OF SALBUTAMOL AND CLENBUTEROL ON SKELETAL-MUSCLE MASS AND CARCASS COMPOSITION IN SENESCENT RATS
COMPARISON OF THE EFFECTS OF SALBUTAMOL AND CLENBUTEROL ON SKELETAL-MUSCLE MASS AND CARCASS COMPOSITION IN SENESCENT RATS
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DOI：
10.1016/0026-0495(94)90054-x
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发表时间：
1994-09-01
影响因子：
9.8
通讯作者：
LYNCH, ME
中科院分区：
文献类型：
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作者：
CARTER, WJ;LYNCH, ME
衰老降低了骨骼肌的质量和强度，使老年受试者特别容易受到年龄相关疾病的分解代谢影响。克伦特罗，肌肉合成代谢β（2）-肾上腺素能激动剂，减少或恢复骨骼肌损失在实验分解代谢状态。然而，在大多数动物模型中用于预防或逆转肌肉萎缩的克仑特罗剂量已经超过了人体的估计安全剂量。最近，另一种β（2）-肾上腺素能激动剂沙丁胺醇（沙丁胺醇）已被证明可以增加年轻大鼠的肌肉重量和蛋白质含量，其剂量与临床使用的剂量相似。与克仑特罗相反，沙丁胺醇目前在美国被批准作为支气管扩张剂用于人类。本研究比较了临床相关剂量的沙丁胺醇与肌肉萎缩动物模型中常用剂量的克仑特罗对肌肉和蛋白质合成代谢的影响。沙丁胺醇和克伦特罗通过植入式渗透微型泵给予3和24个月大的Fischer-344大鼠，剂量为每公斤1.03 mg和600 μ g/24小时，持续3周。测定了5块后肢肌肉的重量以及胴体蛋白质和脂肪含量。沙丁胺醇和克伦特罗增加合并后肢肌肉重量19%和28%，在年轻大鼠，19%和25%的增加老年大鼠。同样，这些药物使年轻大鼠的腓肠肌重量和蛋白质含量增加19%和24%，老年大鼠增加19%和23%。沙丁胺醇和克仑特罗增加胴体蛋白质含量20%和30%，在年轻大鼠，12%和21%的老年大鼠增加。这两种药物增加胴体骨骼肌蛋白质含量计算从胴体肌酸含量在两个年龄。相比之下，这些药物使年轻大鼠的胴体脂肪含量减少了12%和26%，老年大鼠减少了39%和33%。在测试的剂量下，沙丁胺醇引起肌肉重量和蛋白质含量的类似增加，但与克伦特罗相比，胴体蛋白质含量的增加较小。此外，这两种药物似乎都能刺激衰老大鼠在植入泵的应激后肌肉蛋白质损失的恢复。这项研究表明，沙丁胺醇，以及克伦特罗，可能是有用的，在刺激肌肉萎缩的老年人的肌肉生长。因为它目前已被批准用于人类使用，沙丁胺醇可能更容易用于人体试验。版权所有（C）1994由W.B.桑德斯公司
Aging decreases skeletal muscle mass and strength, making elderly subjects particularly vulnerable to catabolic effects of age-related diseases. Clenbuterol, a muscle anabolic beta(2)-adrenergic agonist, has reduced or restored skeletal muscle losses in experimental catabolic states. However, the doses of clenbuterol used to prevent or reverse muscle wasting in most animal models have exceeded the estimated safe dose in man. Recently, another beta(2)-adrenergic agonist, salbutamol (albuterol), has been shown to increase muscle weight and protein content in young rats at a dose similar to that used clinically. In contrast to clenbuterol, salbutamol is currently approved for human use as a bronchodilator in the United States. This study has compared the muscle and protein anabolic effects of salbutamol at a clinically relevant dose with those of clenbuterol at a dose typically used in animal models of muscle wasting. Salbutamol and clenbuterol were administered by implanted osmotic minipumps to Fischer-344 rats aged 3 and 24 months at doses of 1.03 mg and 600 mu g per kilogram per 24 hours for 3 weeks. The weights of five hindlimb muscles, as well as carcass protein and fat content, were determined. Salbutamol and clenbuterol increased combined hindlimb muscle weight 19% and 28% in young rats, with 19% and 25% increases in old rats. Similarly, these drugs increased gastrocnemius weight and protein content 19% and 24% in young rats, with 19% and 23% increases in old rats. Salbutamol and clenbuterol increased carcass protein content 20% and 30% in young rats, with 12% and 21% increases in old rats. Both agents increased carcass skeletal muscle protein content as calculated from carcass creatine content at both ages. In contrast, these agents reduced carcass fat content 12% and 26% in young rats, with 39% and 33% reductions in old rats. At the doses tested, salbutamol caused similar increases in muscle weight and protein content but smaller increases in carcass protein content compared with clenbuterol. In addition, both agents appeared to stimulate recovery of muscle protein lost following the stress of pump implantation in senescent rats. This study suggests that salbutamol, as well as clenbuterol, may be useful in stimulating muscle growth in elderly subjects with muscle wasting. Because it is currently approved for human use, salbutamol may be more readily available for human trial. Copyright (C) 1994 by W.B. Saunders Company