Cartañà J, Segués T, Yebras M, Rothwell N J, Stock M J
Department de Bioquímica i Biotecnologia, Facultat de Ciències Químiques, Universitat Rovira i Virgili, Tarragona, Spain.
Metabolism. 1994 Sep;43(9):1086-92. doi: 10.1016/0026-0495(94)90049-3.
Injection of rats with the beta 2-adrenoceptor agonist clenbuterol (1 mg/kg/d for 15 days) stimulated an increase in body weight (9%) and protein (8%) and water (7%) content, but reduced food intake (4%) and epididymal fat pad mass (39%). Nine days after termination of treatment, ex-clenbuterol rats were heavier (5%) and had a greater protein (7%) and water (6%) content and lower fat pad mass (32%) than controls. Clenbuterol-fed rats (2 mg/kg diet for 10 days, providing an average of 0.04 mg clenbuterol/kg/d) increased body weight (7%), muscle mass (15% to 21%), and muscle protein content (9% to 26%), whereas epididymal fat pad weight and muscle glycogen content were reduced. During the withdrawal period, the greater body weight of ex-clenbuterol rats was sustained overall (ANOVA, P < .00005), but by day 10 this difference was no longer significant. At this point, gastrocnemius muscle mass was still higher (11%) when compared with that of control animals, but soleus muscle mass, muscle glycogen concentration, and epididymal fat pad weight had reverted to control values. These results were corroborated in a subsequent experiment using older rats. It was concluded that, unlike other beta-adrenoceptor-mediated effects, muscle protein accumulated during clenbuterol treatment can be maintained in certain muscles after removal of the drug for a period of time that is at least equivalent to the duration of treatment. This could have implications for the potential therapeutic use of this class of compound, and differences in the response observed between muscle types may help to elucidate the mechanisms responsible for the muscle protein deposition induced by clenbuterol.
给大鼠注射β2肾上腺素能受体激动剂克伦特罗(1毫克/千克/天,持续15天),可刺激体重增加(9%)、蛋白质含量增加(8%)以及水分含量增加(7%),但食物摄入量减少(4%),附睾脂肪垫质量减少(39%)。在治疗终止9天后,曾使用克伦特罗的大鼠比对照组大鼠体重更重(5%),蛋白质含量更高(7%),水分含量更高(6%),脂肪垫质量更低(32%)。用含克伦特罗的饲料喂养大鼠(2毫克/千克饲料,持续10天,平均提供0.04毫克克伦特罗/千克/天),大鼠体重增加(7%),肌肉质量增加(15%至21%),肌肉蛋白质含量增加(9%至26%),而附睾脂肪垫重量和肌肉糖原含量减少。在停药期,曾使用克伦特罗的大鼠总体上保持了较高的体重(方差分析,P <.00005),但到第10天时,这种差异不再显著。此时,与对照动物相比,腓肠肌质量仍更高(11%),但比目鱼肌质量、肌肉糖原浓度和附睾脂肪垫重量已恢复到对照值。在随后使用年龄较大大鼠的实验中证实了这些结果。得出的结论是,与其他β肾上腺素能受体介导的效应不同,在克伦特罗治疗期间积累的肌肉蛋白质在停药一段时间后,至少在与治疗持续时间相当的时间段内,可在某些肌肉中维持。这可能对这类化合物的潜在治疗用途有影响,并且不同肌肉类型之间观察到的反应差异可能有助于阐明克伦特罗诱导肌肉蛋白质沉积的机制。