Analysis of molecular mechanism on the training effects using prohibited doping drugs

盐酸克仑特罗是β -2肾上腺素受体激动剂之一，具有强大的肌肉合成代谢作用，被禁止作为运动员兴奋剂使用。最近有文献表明，肌肉肥大与卫星细胞数量的增加有关，与肌核数量的增加成比例。并且确定了Notch1在卫星细胞中作为肌原性前体细胞从静止状态进入活跃增殖状态时被激活。然而，我们已经报道了Notch 1 mRNA在SOL和EDL中没有变化。此外，盐酸克仑特罗对调节卫星细胞分化的质膜相关细胞质蛋白Numb的影响尚不清楚。在这项研究中，我们试图研究瘦肉精对快肌和慢肌麻木调节系统的肥厚作用。盐酸克仑特罗作为肌生成主调节剂，增加了肌酐的含量，可能导致肌酐进一步肥大，由慢肌酐向快肌酐转变。使用盐酸克仑特罗后，SOL和EDL肌肉湿重均增加。两组肌肉的肌原素mRNA均有所增加。MyoD mRNA在SOL中急剧升高，这可能解释了纤维类型由慢向快转变的快肌纤维的积累，也可能解释了SOL中肌肉的肥大，而EDL中没有。然而，在SOL和EDL中，IGF-1、MGF、Myostatin和Notch1 mRNA没有变化。δ -like1 mRNA在SOL （CLEB: 100.7±20.3%,Control: 100.0±9.5%）中无变化，而在EDL （CLEB: 167.3±28.0%,Control: 100.0±25.0%，P<0.01）中显著升高。在SOL （CLEB: 104.1±19.9%,Control: 100.0±10.3%）中Numb mRNA无明显变化，而在EDL （CLEB: 131.0±20.0%,Control: 100.0±21.5%，P<0.05%）中Numb mRNA显著升高。EDL麻木的增加可能解释了成肌细胞分化的进展导致的肌肉肥大。这些结果表明，药物的肥厚作用应该分别解释为肌纤维或卫星细胞。但像Notch和Numb这样的标记物被称为进展性癌症的标记物。因此，我们有必要研究notch信号系统与兴奋剂致癌过程的关系。少

Clenbuterol is one of the beta-2 adrenergic receptor agonists with powerful muscle anabolic effects and is prohibited to use as doping drug for athletes. Recently it is well documented that the muscle hypertrophy is associated with an increase in satellite cell number, a proportionate increase in myonuclear number. And it is established that Notch1 becomes activated in satellite cells as they progress from a state of quiescence to one of active proliferation as myogenic precursor cells. However, we already reported that the Notch 1 mRNA showed no changes in both SOL and EDL. Furthermore, the effect of clenbuterol on the Numb, a plasma membrane-associated cytoplasmic protein, regulating differentiation of satellite cells is still not clear. In this study, we tried to examine the hypertrophic effects of clenbuterol on the Numb regulating system of both fast-and slow-twitch muscles. It is said that clenbuterol increased the MyoD as the myogenic master regulator and might induce the muscle … More hypertrophy and the transformation from slow-to fast-twitch muscle.The muscle wet weights increased in both SOL and EDL muscles with clenbuterol. The myogenin mRNA showed the increase in both muscles. The MyoD mRNA increased drastically in SOL. They may explained the accumulated fast-twitch fibers with fiber type transition from slow-to-fast and may explain the muscle hypertrophy in SOL, but not in EDL. However, the IGF-1, MGF, Myostatin, and Notch1 mRNA showed no changes in both SOL and EDL. The Delta-like1 mRNA showed no changes in SOL (CLEB: 100.7±20.3%, Control: 100.0±9.5 %), but significantly increased in EDL (CLEB: 167.3±28.0%, Control: 100.0±25.0 %; P<0.01). The Numb mRNA also showed no changes in SOL (CLEB: 104.1±19.9%, Control: 100.0±10.3 %), but significantly increased in EDL (CLEB: 131.0±20.0%, Control: 100.0± 21.5 %; P<0.05%). The increased Numb in EDL may explain the muscle hypertrophy according to progressed differentiation of myoblast. These results suggested that the hypertrophic effects of drugs should be explained in either myofibers or satellite cells, respectively. But these markers like Notch and Numb are known as the markers of progressive cancer. Therefore, we have to examine the relationship with Notch-signaling system and carcinogenic process by doping drugs. Less